Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

Relative adrenal insufficiency in severe congestive heart failure with preserved systolic function: a case report.

PubMed

Lovelock, Joshua D; Coslet, Sandra; Johnson, Marie; Rich, Stuart; Gomberg-Maitland, Mardi

2007-09-01

Relative adrenal insufficiency in critically ill patients is an important syndrome in septic shock. The insufficient stress response of the hypothalamic-pituitary-adrenal axis in acute illness contributes to hemodynamic instability. Treatment of this state in septic shock improves patient outcomes. In this report, we describe the case of a patient with severe diastolic dysfunction who presented in cardiogenic shock associated with relative adrenal insufficiency and had a complete recovery with corticosteroid replacement. Alteration of the hypothalamic-pituitary-adrenal axis may be more prevalent than suspected in end-stage heart failure, and the diagnosis and treatment of this syndrome may ultimately improve outcomes in a subgroup of heart failure patients.

Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach.

PubMed

Rey, R A; Grinspon, R P; Gottlieb, S; Pasqualini, T; Knoblovits, P; Aszpis, S; Pacenza, N; Stewart Usher, J; Bergadá, I; Campo, S M

2013-01-01

Normal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving the gonads and the hypothalamic-pituitary axis. © 2012 American Society of Andrology and European Academy of Andrology.

PITUITARY DEFICIENCY FOLLOWING TRAUMATIC BRAIN INJURY IN EARLY CHILDHOOD: A REVIEW OF THE LITERATURE.

PubMed

Soliman, A T; Adel, A; Soliman, N A; Elalaily, R; De Sanctis, V

2015-01-01

AIMS OF REVIEW: the intent of the current manuscript is to critically review the studies on pituitary gland dysfunction in early childhood following traumatic brain injury (TBI), in comparison with those in adults. Search of the literature: The MEDLINE database was accessed through PubMed in April 2015. Results were restricted to the past 15 years and English language of articles. Both transient and permanent hypopituitarisms are not uncommon after TBI. Early after the TBI, pituitary dysfunction/s differ than those occurring after few weeks and months. Growth hormone deficiency (GHD) and alterations in puberty are the most common. After the one to more years of TBI, pituitary dysfunction tends to improve in some patients but may deteriorate in others. GH deficiency as well as Hypogonadism and thyroid dysfunction are the most common permanent lesions. Many of the symptoms of these endocrine defects can pass unnoticed because of the psychomotor defects associated with the TBI like depression and apathy. Unfortunately pituitary dysfunction appear to negatively affect psycho-neuro-motor recovery as well as growth and pubertal development of children and adolescents after TBI. Therefore, the current review highlights the importance of closely following patients, especially children and adolescents for growth and other symptoms and signs suggestive of endocrine dysfunction. In addition, all should be screened serially for possible endocrine disturbances early after the TBI as well as few months to a year after the injury. Risk factors for pituitary dysfunction after TBI include relatively serious TBI (Glasgow Coma Scale score < 10 and MRI showing damage to the hypothalamic pituitary area), diffuse brain swelling and the occurrence of hypotensive and/or hypoxic episodes. There is a considerable risk of developing pituitary dysfunction after TBI in children and adolescents. These patients should be clinically followed and screened for these abnormalities according to an agreed protocol of investigations. Further multicenter and multidisciplinary prospective studies are required to explore in details the occurrence of permanent pituitary dysfunction after TBI in larger numbers of children with TBI. This requires considerable organisation and communication between many disciplines such as neurosurgery, neurology, endocrinology, rehabilitation and developmental paediatrics.

Alternative causes of hypopituitarism: traumatic brain injury, cranial irradiation, and infections.

PubMed

Pekic, Sandra; Popovic, Vera

2014-01-01

Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic-pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic-pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic-pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease. © 2014 Elsevier B.V. All rights reserved.

Evaluating and Treating Exercise-Related Menstrual Irregularities.

ERIC Educational Resources Information Center

Harmon, Kimberly G.

2002-01-01

Menstrual abnormalities are extremely common in both athletic and non-athletic adolescents and young women. Exercise- related menstrual abnormality is linked with hypothalamic pituitary axis-dysfunction and is a diagnosis of exclusion. In athletes, treatment of secondary menstrual abnormalities and associated health concerns such as bone density…

Reproductive dysfunction and associated pathology in women undergoing military training.

PubMed

Gifford, Robert M; Reynolds, R M; Greeves, J; Anderson, R A; Woods, D R

2017-10-01

Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long-term subfertility. A critical review of pertinent evidence following an extensive literature search. The evidence points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests that reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training, this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. We identify lines of future research to more fully characterise reproductive dysfunction in military women and suggest possible interventions that, if indicated, could improve their future well-being. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Non-analgesic effects of opioids: opioids and the endocrine system.

PubMed

Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

2012-01-01

Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis.

PubMed

Gonzalez Rozas, Marta; Hernanz Roman, Lidia; Gonzalez, Diego Gonzalez; Pérez-Castrillón, José Luis

2016-01-01

Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis

PubMed Central

Gonzalez Rozas, Marta; Hernanz Roman, Lidia; Gonzalez, Diego Gonzalez; Pérez-Castrillón, José Luis

2016-01-01

Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism. PMID:27213061

The physiology of functional hypothalamic amenorrhea associated with energy deficiency in exercising women and in women with anorexia nervosa.

PubMed

Allaway, Heather C M; Southmayd, Emily A; De Souza, Mary Jane

2016-02-01

An energy deficiency is the result of inadequate energy intake relative to high energy expenditure. Often observed with the development of an energy deficiency is a high drive for thinness, dietary restraint, and weight and shape concerns in association with eating behaviors. At a basic physiologic level, a chronic energy deficiency promotes compensatory mechanisms to conserve fuel for vital physiologic function. Alterations have been documented in resting energy expenditure (REE) and metabolic hormones. Observed metabolic alterations include nutritionally acquired growth hormone resistance and reduced insulin-like growth factor-1 (IGF-1) concentrations; hypercortisolemia; increased ghrelin, peptide YY, and adiponectin; and decreased leptin, triiodothyronine, and kisspeptin. The cumulative effect of the energetic and metabolic alterations is a suppression of the hypothalamic-pituitary-ovarian axis. Gonadotropin releasing hormone secretion is decreased with consequent suppression of luteinizing hormone and follicle stimulating hormone release. Alterations in hypothalamic-pituitary secretion alters the production of estrogen and progesterone resulting in subclinical or clinical menstrual dysfunction.

Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning.

PubMed

Gandhi, Jason; Hernandez, Rafael J; Chen, Andrew; Smith, Noel L; Sheynkin, Yefim R; Joshi, Gargi; Khan, Sardar Ali

2017-04-01

Lead poisoning is a stealthy threat to human physiological systems as chronic exposure can remain asymptomatic for long periods of time before symptoms manifest. We presently review the biophysical mechanisms of lead poisoning that contribute to male infertility. Environmental and occupational exposure of lead may adversely affect the hypothalamic-pituitary-testicular axis, impairing the induction of spermatogenesis. Dysfunction at the reproductive axis, namely testosterone suppression, is most susceptible and irreversible during pubertal development. Lead poisoning also appears to directly impair the process of spermatogenesis itself as well as sperm function. Spermatogenesis issues may manifest as low sperm count and stem from reproductive axis dysfunction or testicular degeneration. Generation of excessive reactive oxygen species due to lead-associated oxidative stress can potentially affect sperm viability, motility, DNA fragmentation, membrane lipid peroxidation, capacitation, hyperactivation, acrosome reaction, and chemotaxis for sperm-oocyte fusion, all of which can contribute to deter fertilization. Reproductive toxicity has been tested through cross-sectional analysis studies in humans as well as in vivo and in vitro studies in animals.

Hypothalamic demyelination causing panhypopituitarism.

PubMed

Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

2018-05-01

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

PubMed

Johnson, Elizabeth O; Calogero, Aldo E; Konstandi, Maria; Kamilaris, Themis C; La Vignera, Sandro; Vignera, Sandro La; Chrousos, George P

2013-06-01

Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury.

PubMed

Reifschneider, Kent; Auble, Bethany A; Rose, Susan R

2015-07-31

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

PubMed Central

Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

2015-01-01

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

Imaging of pediatric pituitary endocrinopathies

PubMed Central

Chaudhary, Vikas; Bano, Shahina

2012-01-01

Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

PubMed

Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

2005-07-01

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.

PubMed

Osterstock, Guillaume; El Yandouzi, Taoufik; Romanò, Nicola; Carmignac, Danielle; Langlet, Fanny; Coutry, Nathalie; Guillou, Anne; Schaeffer, Marie; Chauvet, Norbert; Vanacker, Charlotte; Galibert, Evelyne; Dehouck, Bénédicte; Robinson, Iain C A F; Prévot, Vincent; Mollard, Patrice; Plesnila, Nikolaus; Méry, Pierre-François

2014-05-01

Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

[The relationship between neuroendocrine dysfunction and free-radical oxidation in old age alcoholism].

PubMed

Vinogradov, D B; Mingazov, A Kh; Izarovskaya, I V; Babin, K A; Sinitsky, A I

2015-01-01

to study the relationship between dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and free-radical oxidation in old age alcoholism. Authors examined 46 men and women, aged 60-80 years, with alcoholism. Contents of cortisol, lipid peroxidation products and the level of an oxidatively modified protein were measured. A decrease in blood cortisol content and correlations between its level and activity of free-radical oxidation were identified. The severity of neuroendocrine dysfunction in old patients was sex-related. It has been suggested that the impairment of HPA system activity may be a cause of oxidative stress and development of alcoholism.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

PubMed

Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan; Thomas, Theresa C

2016-07-01

As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. © 2016 The authors.

Time Course of Symptomatic Recovery After Endoscopic Transsphenoidal Surgery for Pituitary Adenoma Apoplexy in the Modern Era.

PubMed

Zaidi, Hasan A; Cote, David J; Burke, William T; Castlen, Joseph P; Bi, Wenya Linda; Laws, Edward R; Dunn, Ian F

2016-12-01

Pituitary tumor apoplexy can result from either hemorrhagic or infarctive expansion of pituitary adenomas, and the related mass effect can result in compression of critical neurovascular structures. The time course of recovery of visual field deficits, headaches, ophthalmoparesis, and pituitary dysfunction after endoscopic transsphenoidal surgery has not been well established. Medical records were retrospectively reviewed for all patients who underwent endoscopic transsphenoidal surgery for pituitary tumor apoplexy from April 2008 to November 2014. Of 578 patients who underwent transsphenoidal surgery, pituitary tumor apoplexy was identified in 44 patients (7.6%). Two patients had prior surgery, leaving 42 patients for final analysis. These included infarction-related apoplexy in 7 (14.4%) patients, and hemorrhagic apoplexy in 35 (85.6%) patients. Hemorrhagic adenomas had a larger axial tumor diameter than patients with infarctive adenomas (4.4 ± 4.1 cm vs. 1.8 ± 0.8 cm; P < 0.01), but were otherwise equivalent. At an average last follow-up of 2.52 years (range, 0.1-6.7 years), resolution of ophthalmoparesis as a result of pituitary tumor apoplexy demonstrated the longest recovery course (range, 2.4 ± 2.2 months) compared with visual field deficits (range, 8.0 ± 9.9 days), headaches (range, 1.9 ± 3.0 days), or pituitary dysfunction (range, 2.0 ± 1.8 weeks; P < 0.01). All patients who presented with headaches (n = 37) and/or visual disturbances (n = 22) had complete resolution of symptoms at last follow-up, whereas 83.3% of patients who presented with ophthalmoplegia experienced resolution. Endocrinologic dysfunction remained relatively consistent after surgery. Endoscopic transsphenoidal surgery can provide durable resolution of symptoms for patients presenting with pituitary tumor apoplexy. Recovery from headaches, visual, and pituitary dysfunction may be more rapid compared with ophthalmoparesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

PubMed Central

Cheung, Leonard Y. M.; Okano, Hideyuki

2016-01-01

The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. PMID:27616671

Pathophysiology of hypopituitarism in the setting of brain injury

PubMed Central

Dusick, Joshua R.; Wang, Christina; Cohan, Pejman; Swerdloff, Ronald

2014-01-01

The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. PMID:18481181

20 years of leptin: role of leptin in human reproductive disorders.

PubMed

Chou, Sharon H; Mantzoros, Christos

2014-10-01

Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin. © 2014 Society for Endocrinology.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Pituitary Medicine From Discovery to Patient-Focused Outcomes

PubMed Central

2016-01-01

Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility

PubMed Central

Carta, Gaspare; Artini, Paolo Giovanni

2016-01-01

Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed. PMID:27559343

Telomeres and endocrine dysfunction of the adrenal and GH/IGF-1 axes.

PubMed

Aulinas, Anna; Ramírez, María José; Barahona, María José; Mato, Eugènia; Bell, Olga; Surrallés, Jordi; Webb, Susan M

2013-12-01

Telomeres, located at the end of linear chromosomes, are essential to maintain genomic stability. Telomere biology has recently emerged as an important player in the fields of ageing and disease. To maintain telomere length (TL) and reduce its degradation after mitosis, the telomerase enzyme complex is produced. Genetic, epigenetic, hormonal and environmental factors can regulate telomerase function. These include stress hormones such as cortisol and growth factors. The hypothalamic-pituitary-adrenal (HPA) axis has been evaluated in psychiatric diseases where hypercortisolism and oxidative stress are often present. Some researches have linked TL shortening to increases in stress-related cortisol, but others have not. The effects of cortisol on the telomere system are complex and may depend on the intensity and duration of exposure. On the other hand, low levels of IGF-1 are associated with inflammation and ageing-related diseases (ischaemic heart disease, congestive heart failure). Both IGF-1 and TL diminish with age and are positively and strongly correlated with each other. It is not clear whether this positive correlation reflects a single association or a cause-effect relationship. Further research will ideally investigate longitudinal changes in telomeres and both these hormonal axes. To our knowledge, TL dysfunction has not been described in either endogenous hypercortisolism (Cushing's syndrome) or acromegaly where excessive amounts of GH and consequently IGF-1 are produced. This review focuses on the possible relationships between telomere dysfunction and the hypothalamic-pituitary-adrenal (HPA) axis and GH-IGF-1 system. © 2013 John Wiley & Sons Ltd.

Ischemic and oxidative damage to the hypothalamus may be responsible for heat stroke.

PubMed

Chen, Sheng-Hsien; Lin, Mao-Tsun; Chang, Ching-Ping

2013-03-01

The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

PubMed

Ntali, Georgia; Wass, John A

2018-04-01

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

Purinergic signaling pathways in endocrine system.

PubMed

Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

2015-09-01

Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

Purinergic Signaling Pathways in Endocrine System

PubMed Central

Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

2015-01-01

Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

Craniopharyngioma in Children: Long-term Outcomes

PubMed Central

STEINBOK, Paul

2015-01-01

The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

Hypopituitarism after traumatic brain injury.

PubMed

Bondanelli, Marta; Ambrosio, Maria Rosaria; Zatelli, Maria Chiara; De Marinis, Laura; degli Uberti, Ettore C

2005-05-01

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.

Hypocretin-1 deficiency in a girl with ROHHAD syndrome.

PubMed

Dhondt, Karlien; Verloo, Patrick; Verhelst, Hélène; Van Coster, Rudy; Overeem, Sebastiaan

2013-09-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and complex pediatric syndrome, essentially caused by dysfunction of 3 vital systems regulating endocrine, respiratory, and autonomic nervous system functioning. The clinical spectrum of ROHHAD is broad, but sleep/wake disorders have received relatively little attention so far, although the central hypothalamic dysfunction would make the occurrence of sleep symptoms likely. In this case report, we expand the phenotype of ROHHAD with a number of striking sleep symptoms that together can be classified as a secondary form of narcolepsy. We present a 7-year-old girl with ROHHAD who displayed the classic features of narcolepsy with cataplexy: excessive daytime sleepiness with daytime naps, visual hallucinations, and partial cataplexy reflected in intermittent loss of facial muscle tone. Nocturnal polysomnography revealed sleep fragmentation and a sleep-onset REM period characteristic for narcolepsy. The diagnosis was confirmed by showing an absence of hypocretin-1 in the cerebrospinal fluid. We discuss potential pathophysiological implications as well as symptomatic treatment options.

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

PubMed

Sillem, M; Rabe, T; Runnebaum, B

1997-01-01

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Management of prolactinomas.

PubMed

Molitch, M E

1989-01-01

Prolactinomas are the most common of the hormone-secreting pituitary tumors and must be distinguished from nonsecreting tumors causing hyperprolactinemia by hypothalamic or stalk dysfunction. For both micro- and macroadenomas, dopamine agonists appear to be the treatment of choice, transsphenoidal surgery being reserved for nonresponders. For women desiring pregnancy, dopamine agonists are safe when there is a microadenoma or an intrasellar macroadenoma. However, in women with large macroadenomas desiring pregnancy, limited transsphenoidal decompression followed by bromocriptine appears to be the safest mode of treatment.

Decreased hypothalamus volumes in generalized anxiety disorder but not in panic disorder.

PubMed

Terlevic, Robert; Isola, Miriam; Ragogna, Maria; Meduri, Martina; Canalaz, Francesca; Perini, Laura; Rambaldelli, Gianluca; Travan, Luciana; Crivellato, Enrico; Tognin, Stefania; Como, Giuseppe; Zuiani, Chiara; Bazzocchi, Massimo; Balestrieri, Matteo; Brambilla, Paolo

2013-04-25

The hypothalamus is a brain structure involved in the neuroendocrine aspect of stress and anxiety. Evidence suggests that generalized anxiety disorder (GAD) and panic disorder (PD) might be accompanied by dysfunction of the hypothalamus-pituitary-adrenal axis (HPA), but so far structural alterations were not studied. We investigated hypothalamic volumes in patients with either GAD or PD and in healthy controls. Twelve GAD patients, 11 PD patients and 21 healthy controls underwent a 1.5T MRI scan. Hypothalamus volumes were manually traced by a rater blind to subjects' identity. General linear model for repeated measures (GLM-RM) was used to compare groups on hypothalamic volumes, controlling for total intracranial volume, age and sex. The hypothalamus volume was significantly reduced (p=0.04) in GAD patients, with significant reductions in both the left (p=0.02) and right side (p=0.04). Patients with PD did not differ significantly (p=0.73). Anxiety scores were inversely correlated with hypothalamic volumes. The small sample size could reduce the generalizability of the results while the lack of stress hormone measurements renders functional assessment of the hypothalamus-pituitary-adrenal axis not feasible. The present study showed decreased hypothalamic volumes in GAD patients but not in those with PD. Future longitudinal studies should combine volumetric data with measurements of stress hormones to better elucidate the role of the HPA axis in GAD. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity.

PubMed

Krajnak, K; Sriram, K; Johnson, C; Roberts, J R; Mercer, R; Miller, G R; Wirth, O; Antonini, J M

2017-01-01

Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl 2 ). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction.

Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

PubMed

Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

2015-05-01

The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Primary treatment regimen and diabetes insipidus as predictors of health outcomes in adults with childhood-onset craniopharyngioma.

PubMed

Yuen, Kevin C J; Kołtowska-Häggström, Maria; Cook, David M; Fox, Janet L; Jönsson, Peter J; Geffner, Mitchell E; Abs, Roger

2014-04-01

Craniopharyngiomas are often associated with significant morbidity due to their location and treatment effects. Little is known of the effects of primary treatment regimen and diabetes insipidus (DI), a clinical surrogate of hypothalamic obesity, on health outcomes in adults with childhood-onset craniopharyngioma (COCP). The objective of the study was to examine health outcomes of adults with COCP based on primary treatment regimens and the presence of DI. This study included a retrospective KIMS (Pfizer International Metabolic Database) data analysis of 180 adults with COCP according to the primary treatment regimen [one surgery (1Surg) vs complex treatment regimen (CTrR) of more than 1Surg and/or radiotherapy] and the presence of DI. The majority of COCP patients underwent transcranial surgery (77%) without receiving radiotherapy (84%). Compared with the 1Surg group, more CTrR patients developed visual field defects and ophthalmoplegia (all P < .01). Compared with patients without DI, those with DI had higher rates of anterior pituitary hormone deficits, body mass index, and fat mass (all P < .01). By contrast, fasting glucose, hemoglobin A1c, lipid panel, and quality of life were comparable among 1Surg vs CTrR patients, and patients with vs without DI. Regardless of primary treatment received, the presence of DI in either group was associated with higher rates of anterior pituitary hormone deficits and obesity. CTrR and DI predicted health outcomes differently. CTrR predisposed to the development of visual dysfunction, whereas DI was associated with higher rates of anterior pituitary dysfunction and weight gain. Higher body mass index and fat mass in patients with DI further implicate the role of hypothalamic damage as an important causal factor of obesity in these patients.

Endocrine changes in histiocytosis of the hypothalamic-pituitary axis.

PubMed

Toro Galván, Silvia; Planas Vilaseca, Alejandra; Michalopoulou Alevras, Theodora; Torres Díaz, Alberto; Suárez Balaguer, Javier; Villabona Artero, Carles

2015-02-01

Histiocytosis is characterized by proliferation of cells from the mononuclear phagocyte system, and may be divided into Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (including Erdheim-Chester disease [ECD]). While diabetes insipidus (DI) is the most common hypothalamic-pituitary consequence, anterior pituitary deficiencies are less known. This study analyzed the frequency and progression of pituitary hormone deficiencies and the radiographic findings in 9 patients (7 with LCH and 2 with ECD) with hypothalamic-pituitary (HP) axis. Eighty-nine percent of patients had DI (62% at diagnosis), and 78% had one or more anterior pituitary deficiencies (71% at diagnosis). HP involvement is relatively common in patients diagnosed with histiocytosis and hormone deficiencies may be present at diagnosis or appear gradually during the course of disease. Regular monitoring of these patients is recommended. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response.

PubMed

Sominsky, Luba; Ziko, Ilvana; Spencer, Sarah J

2017-01-01

The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting directly at the anterior pituitary where the growth hormone secretagogue receptor (GHSR), the receptor for acyl ghrelin, is abundantly expressed. We therefore hypothesised that neonatal overfeeding in female rats would compromise pituitary responsiveness to ghrelin, contributing to a hyperactive central stress responsiveness. Unlike in males where hypothalamic ghrelin signalling is compromised by neonatal overfeeding, there was no effect of early life diet on circulating ghrelin or hypothalamic ghrelin signalling in females, indicating hypothalamic feeding and metabolic ghrelin circuitry remains intact. However, neonatal overfeeding did lead to long-term alterations in the pituitary ghrelin system. The neonatally overfed females had increased neonatal and reduced adult expression of GHSR and ghrelin-O-acyl transferase (GOAT) in the pituitary as well as reduced pituitary responsiveness to exogenous acyl ghrelin-induced adrenocorticotropic hormone (ACTH) release in vitro. These data suggest that neonatal overfeeding dysregulates pituitary ghrelin signalling long-term in females, potentially accounting for the hyper-responsive HPA axis in these animals. These findings have implications for how females may respond to stress throughout life, suggesting the way ghrelin modifies the stress response at the level of the pituitary may be less efficient in the neonatally overfed.

Prevalence and Predictors of Overweight and Obesity in Patients with Pituitary Dysfunctions.

PubMed

Harbeck, Birgit; Danneberg, Sven; Rahvar, Amir-Hossein; Monig, Heiner; Haas, Christian S

2016-01-01

Patients with hypothalamic-pituitary disorders (HPD) may be of increased risk to develop overweight and obesity, thereby fostering cardiovascular events. However, it remains unclear if patients with pituitary dysfunctions per se have an increased risk of becoming obese. The objective of this study was to evaluate prevalence and to identify possible predictors of overweight and obesity in patients with pituitary dysfunctions. A total of 121 out-patients having various causes for HPD were assessed for height and body weight; body mass index (BMI) was calculated and correlated with clinical features. Patients were divided into various subgroups depending on underlying conditions and therapeutic modalities. Most of the HPD patients were overweight or obese with males being significantly more affected. Of interest, patients with macroadenomas suffered significantly more often from overweight and obesity than individuals with microadenomas (73.4% vs. 43.5%, p= 0.006). Increased BMI (≥25 kg/m2) tended to be more common in patients with prolactinomas (70.0%), hormone deficiencies (76.1%) and hormone replacement therapies (76.6%) than in a healthy population. In conclusion, we showed that patients with HPD: (i) frequently suffer from overweight and obesity; (ii) prevalence of overweight and obesity however is comparable to that in the general population; (iii) only patients with macroadenomas seem to have a significantly higher risk; (iv) hormone deficiencies and hormonal replacement therapy may foster weight gain and (v) radiation and surgical tumour therapy per se do not seem to be additional risk factors for weight gain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

PubMed

van Norren, Klaske; Dwarkasing, Jvalini T; Witkamp, Renger F

2017-09-01

In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

Impaired hypothalamic regulation of endocrine function and delayed counterregulatory response to hypoglycemia in Magel2-null mice.

PubMed

Tennese, Alysa A; Wevrick, Rachel

2011-03-01

Hypothalamic dysfunction may underlie endocrine abnormalities in Prader-Willi syndrome (PWS), a genetic disorder that features GH deficiency, obesity, and infertility. One of the genes typically inactivated in PWS, MAGEL2, is highly expressed in the hypothalamus. Mice deficient for Magel2 are obese with increased fat mass and decreased lean mass and have blunted circadian rhythm. Here, we demonstrate that Magel2-null mice have abnormalities of hypothalamic endocrine axes that recapitulate phenotypes in PWS. Magel2-null mice had elevated basal corticosterone levels, and although male Magel2-null mice had an intact corticosterone response to restraint and to insulin-induced hypoglycemia, female Magel2-null mice failed to respond to hypoglycemia with increased corticosterone. After insulin-induced hypoglycemia, Magel2-null mice of both sexes became more profoundly hypoglycemic, and female mice were slower to recover euglycemia, suggesting an impaired hypothalamic counterregulatory response. GH insufficiency can produce abnormal body composition, such as that seen in PWS and in Magel2-null mice. Male Magel2-null mice had Igf-I levels similar to control littermates. Female Magel2-null mice had low Igf-I levels and reduced GH release in response to stimulation with ghrelin. Female Magel2-null mice did respond to GHRH, suggesting that their GH deficiency has a hypothalamic rather than pituitary origin. Female Magel2-null mice also had higher serum adiponectin than expected, considering their increased fat mass, and thyroid (T(4)) levels were low. Together, these findings strongly suggest that loss of MAGEL2 contributes to endocrine dysfunction of hypothalamic origin in individuals with PWS.

The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

PubMed Central

Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

2009-01-01

Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

Adaptive Response in Female Modeling of the Hypothalamic-pituitary-gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder

PubMed Central

Vasconcelos-Moreno, Mirela Paiva; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Sartori, Juliana; Eisele, Bárbara; Ferrari, Pamela; Fijtman, Adam; Rüegg, Joëlle; Gassen, Nils Christian; Kapczinski, Flávio; Rein, Theo; Kauer-Sant’Anna, Márcia

2015-01-01

Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness. PMID:25522387

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response

PubMed Central

Ziko, Ilvana; Spencer, Sarah J.

2017-01-01

The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting directly at the anterior pituitary where the growth hormone secretagogue receptor (GHSR), the receptor for acyl ghrelin, is abundantly expressed. We therefore hypothesised that neonatal overfeeding in female rats would compromise pituitary responsiveness to ghrelin, contributing to a hyperactive central stress responsiveness. Unlike in males where hypothalamic ghrelin signalling is compromised by neonatal overfeeding, there was no effect of early life diet on circulating ghrelin or hypothalamic ghrelin signalling in females, indicating hypothalamic feeding and metabolic ghrelin circuitry remains intact. However, neonatal overfeeding did lead to long-term alterations in the pituitary ghrelin system. The neonatally overfed females had increased neonatal and reduced adult expression of GHSR and ghrelin-O-acyl transferase (GOAT) in the pituitary as well as reduced pituitary responsiveness to exogenous acyl ghrelin-induced adrenocorticotropic hormone (ACTH) release in vitro. These data suggest that neonatal overfeeding dysregulates pituitary ghrelin signalling long-term in females, potentially accounting for the hyper-responsive HPA axis in these animals. These findings have implications for how females may respond to stress throughout life, suggesting the way ghrelin modifies the stress response at the level of the pituitary may be less efficient in the neonatally overfed. PMID:28282447

Adaptive Responses to Prochloraz Exposure in the Hypothalamic-Pituitary Gonadal Axis of Fathead Minnows

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course ...

A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.

PubMed

Whirledge, Shannon; Cidlowski, John A

2013-12-01

In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

PubMed Central

Whirledge, Shannon

2013-01-01

In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success. PMID:24064362

Craniopharyngioma

PubMed Central

Garnett, Matthew R; Puget, Stéphanie; Grill, Jacques; Sainte-Rose, Christian

2007-01-01

Craniopharyngiomas are benign slow growing tumours that are located within the sellar and para sellar region of the central nervous system. The point prevalence of this tumour is approximately 2/100,000. The onset of symptoms is normally insidious with most patients at diagnosis having neurological (headaches, visual disturbances) and endocrine (growth retardation, delayed puberty) dysfunctions. Craniopharyngiomas are thought to arise from epithelial remnants of the craniopharyngeal duct or Rathke's pouch (adamantinomatous type) or from metaplasia of squamous epithelial cell rests that are remnants of the part of the stomadeum that contributed to the buccal mucosa (squamous papillary type). The neuroradiological diagnosis is mainly based on the three components of the tumour (cystic, solid and calcified) in the characteristic sellar/para sellar location. Definitive diagnosis is made following histological examination of a surgical specimen. The differential diagnosis includes other tumours in this region (pituitary adenoma), infectious or inflammatory processes (eosinophilic granuloma), vascular malformations (aneurysm) and congenital anomalies (Rathke's cleft cyst). The current treatment is gross total excision of the tumour, if there is no hypothalamic invasion or, in the presence of hypothalamic invasion, a sub-total resection with post-operative radiotherapy. Endocrine disturbances are normally permanent and need careful replacement. Overall, there is an 80% 5 year survival, though this can be associated with marked morbidity (hypothalamic dysfunction, altered neuropsychological profile). PMID:17425791

A case of atypical McCune-Albright syndrome requiring optic nerve decompression.

PubMed

Yavuzer, R; Khilnani, R; Jackson, I T; Audet, B

1999-10-01

McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of café-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented.

Predicting Adaptive Response to Fadrozole Exposure:Computational Model of the Fathead MinnowsHypothalamic-Pituitary-Gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (...

Novel FGF8 Mutations Associated with Recessive Holoprosencephaly, Craniofacial Defects, and Hypothalamo-Pituitary Dysfunction

PubMed Central

McCabe, Mark J.; Gaston-Massuet, Carles; Tziaferi, Vaitsa; Gregory, Louise C.; Alatzoglou, Kyriaki S.; Signore, Massimo; Puelles, Eduardo; Gerrelli, Dianne; Farooqi, I. Sadaf; Raza, Jamal; Walker, Joanna; Kavanaugh, Scott I.; Tsai, Pei-San; Pitteloud, Nelly; Martinez-Barbera, Juan-Pedro

2011-01-01

Context: Fibroblast growth factor (FGF) 8 is important for GnRH neuronal development with human mutations resulting in Kallmann syndrome. Murine data suggest a role for Fgf8 in hypothalamo-pituitary development; however, its role in the etiology of wider hypothalamo-pituitary dysfunction in humans is unknown. Objective: The objective of this study was to screen for FGF8 mutations in patients with septo-optic dysplasia (n = 374) or holoprosencephaly (HPE)/midline clefts (n = 47). Methods: FGF8 was analyzed by PCR and direct sequencing. Ethnically matched controls were then screened for mutated alleles (n = 480–686). Localization of Fgf8/FGF8 expression was analyzed by in situ hybridization in developing murine and human embryos. Finally, Fgf8 hypomorphic mice (Fgf8loxPNeo/−) were analyzed for the presence of forebrain and hypothalamo-pituitary defects. Results: A homozygous p.R189H mutation was identified in a female patient of consanguineous parentage with semilobar HPE, diabetes insipidus, and TSH and ACTH insufficiency. Second, a heterozygous p.Q216E mutation was identified in a female patient with an absent corpus callosum, hypoplastic optic nerves, and Moebius syndrome. FGF8 was expressed in the ventral diencephalon and anterior commissural plate but not in Rathke's pouch, strongly suggesting early onset hypothalamic and corpus callosal defects in these patients. This was consolidated by significantly reduced vasopressin and oxytocin staining neurons in the hypothalamus of Fgf8 hypomorphic mice compared with controls along with variable hypothalamo-pituitary defects and HPE. Conclusion: We implicate FGF8 in the etiology of recessive HPE and potentially septo-optic dysplasia/Moebius syndrome for the first time to our knowledge. Furthermore, FGF8 is important for the development of the ventral diencephalon, hypothalamus, and pituitary. PMID:21832120

Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

Adaptive Response in Female Fathead Minnows Exposed to an Aromatase Inhibitor: Computational Modeling of the Hypothalamic-Pituitary-Gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

Charcterization of the Hypothalamic-Pituitary-Adrenal Axis Response to Atrazine and Metabolites in the Female Rat

EPA Science Inventory

Atrazine (ATR) has recently been shown to activate the hypothalamic-pituitary-adrenal (HPA) axis in rodents. The current study investigated the effect of ATR and two of its chlorinated metabolites, desisopropylatrazine (DIA) and diamino-s-chlorotriazine (DACT), on the HPA axis in...

MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings.

PubMed

Miller, L; Angulo, M; Price, D; Taneja, S

1996-01-01

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.

Biological mechanisms of premature ovarian failure caused by psychological stress based on support vector regression

PubMed Central

Wang, Xiu-Feng; Zhang, Lei; Wu, Qing-Hua; Min, Jian-Xin; Ma, Na; Luo, Lai-Cheng

2015-01-01

Psychological stress has become a common and important cause of premature ovarian failure (POF). Therefore, it is very important to explore the mechanisms of POF resulting from psychological stress. Sixty SD rats were randomly divided into control and model groups. Biomolecules associated with POF (β-EP, IL-1, NOS, NO, GnRH, CRH, FSH, LH, E2, P, ACTH, and CORT) were measured in the control and psychologically stressed rats. The regulation relationships of the biomolecules were explored in the psychologically stressed state using support vector regression (SVR). The values of β-EP, IL-1, NOS, and GnRH in the hypothalamus decreased significantly, and the value of NO changed slightly, when the values of 3 biomolecules in the hypothalamic-pituitary-adrenal axis decreased. The values of E2 and P in the hypothalamic-pituitary-ovarian axis decreased significantly, while the values of FSH and LH changed slightly, when the values of the biomolecules in the hypothalamus decreased. The values of FSH and LH in the pituitary layer of the hypothalamic-pituitary-ovarian axis changed slightly when the values of E2 and P in the target gland layer of the hypothalamic-pituitary-ovarian axis decreased. An Imbalance in the neuroendocrine-immune bimolecular network, particularly the failure of the feedback action of the target gland layer to pituitary layer in the pituitary-ovarian axis, is possibly one of the pathogenic mechanisms of POF. PMID:26885082

Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

ERIC Educational Resources Information Center

Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

2015-01-01

Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals

EPA Science Inventory

There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...

A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole on components of the hypothalamic-pituitary-gonadal axis of fathead minnows (Presentation)

EPA Science Inventory

The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

Transcriptional regulatory dynamics of the hypothalamic-pituitary-gonadal axis and its peripheral pathways as impacted by the 3-beta HSD inhibitor Trilostane in zebrafish (Danio rerio)

EPA Science Inventory

To identify transcription factors (TFs), members of hypothalamic-pituitary- gonadal axis (HPG-axis), TF networks and signaling pathways underlying generalized effects of 3-beta hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exp...

Computational Modeling of Hypothalamic-Pituitary-Gonadal Axis to Predict Adaptive Responses in Female Fathead Minnows Exposed to an Aromatase Inhibitor

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose response and time-course...

A Time-course Analysis of Effects of the Steroidogenesis Inhibitor Ketoconazole on Components of the Hypothalamic-pituitary-gonadal Axis of Fathead Minnows

EPA Science Inventory

The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

A Time-course Analysis of Effects of the Steroidogenesis Inhibitor Ketoconazole on Components of the Hypothalamic-pituitary-gonadal Axis of Fathead Minnows

EPA Science Inventory

The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconaz...

Diabetes Insipidus after Traumatic Brain Injury

PubMed Central

Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki

2015-01-01

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685

Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

PubMed

Berga, Sarah L; Loucks, Tammy L

2006-12-01

Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes, such as cognitive behavior therapy (CBT), have the potential to permit resumption of full ovarian function along with recovery of the adrenal, thyroidal, and other neuroendocrine aberrations. Full endocrine recovery potentially offers better individual, maternal, and child health.

Fine morphological evaluation of hypothalamus in patients with hyperphagia.

PubMed

Ogawa, Yoshikazu; Niizuma, Kuniyasu; Tominaga, Teiji

2017-05-01

Various metabolic diseases induced by eating disorders are some of the most serious and difficult problems for modern public healthcare. However, little is known about hyperphagia, partly because of the lack of a clear definition. Several basic studies have analyzed eating habits using endocrinological or neurophysiological approaches, which have suggested a controlled balance between the hunger and satiety centers in the central nervous system. However, more detailed neuro-radiologic evaluations have not been achieved for the hypothalamus, and evaluations were limited only to the floor of the third ventricles. Fine structures of hypothalamic morphology were investigated using high-resolution magnetic resonance imaging in seven patients with hypothalamo-pituitary tumors, who suffered from preoperative hyperphagia-induced severe obesity and metabolic disorders. Body mass index (BMI) varied from 22.4 to 40.5 kg/m 2 (mean 32.8 kg/m 2 ). Clinical data were compared with the data of nine patients without hyperphagia and seven healthy volunteers. Morphological evaluation was possible in all patients and control subjects, and patients with hyperphagia had significantly shortened maximum distances between the ependymal layers of the lateral wall of the third ventricle and fornixes (hyperphagia group right side 0.30 mm, left side 0.23 mm vs. patients without hyperphagia group right side 1.60, left side 1.53 vs. healthy group right side 1.73 mm, left side 1.85 mm) (p < 0.01). Two patients achieved postoperative improvement in both clinical and neuro-radiological findings. Eating and metabolic disorders are related to strong dysfunction of the medial nuclei of the hypothalamus in patients with hypothalamo-pituitary tumors. We report the first case of dynamic improvement from hyperphagia, with both symptomatic and neuro-radiological findings.

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

PubMed

Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

2017-10-15

Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: a case report.

PubMed

Jung, Dai; Seo, Go Hun; Kim, Yoon-Myung; Choi, Jin-Ho; Yoo, Han-Wook

2018-03-01

Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.

Resveratrol ameliorated the behavioral deficits in a mouse model of post-traumatic stress disorder.

PubMed

Zhang, Ze-Shun; Qiu, Zhi-Kun; He, Jia-Li; Liu, Xu; Chen, Ji-Sheng; Wang, Yu-Lu

2017-10-01

Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction. Copyright © 2017. Published by Elsevier Inc.

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

PubMed

Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats.

PubMed

Sun, Jianran; Hui, Cancan; Xia, Tongjia; Xu, Min; Deng, Datong; Pan, Faming; Wang, Youmin

2018-05-24

This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

A study of temporal effects of the model anti-androgen flutamide on components of the hypothalamic-pituitary-gonadal axis in adult fathead minnows

EPA Science Inventory

The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnow (Pimephales promelas) treated with the model androgen receptor (AR) antagonist, flutamide. Reproductively-mature fish were exposed in a flow-through, meas...

Assessment of Diverse Biological Indicators in Gulf War Illness: Are They Replicable Are They Related

DTIC Science & Technology

2016-04-01

compared to 50 healthy veteran controls in a protocol that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI, DTI), adrenal...SUBJECT TERMS Gulf War illness, neuroimaging, neuropsychological testing, immune function, hypothalamic-pituitary-adrenal testing 16. SECURITY... neuropsychological evaluations, assessment of hypothalamic-pituitary-adrenal function, standard clinical diagnostic laboratory tests, and research

If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

ERIC Educational Resources Information Center

Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

2007-01-01

The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

LOW-DOSE EFFECTS OF AMMONIUM PERCHLORATE ON THE HYPOTHALAMIC-PITUITARY-THYROID (HPT) AXIS OF ADULT MALE RATS PRETREATED WITH PCB126

EPA Science Inventory

The objective of this research was to characterize the disturbances in the hypothalamic-pituitary-thyroid (HPT) axis resulting from exposure to a binary mixture, 3,3',4',5-pentachlorobiphenyl (PCB126) and perchlorate (ClO_4 ), known to cause hypothyroid-ism by different modes of...

Mindful Parenting Predicts Mothers' and Infants' Hypothalamic-Pituitary-Adrenal Activity during a Dyadic Stressor

ERIC Educational Resources Information Center

Laurent, Heidemarie K.; Duncan, Larissa G.; Lightcap, April; Khan, Faaiza

2017-01-01

Mindfulness in the parenting relationship has been proposed to help both parents and children better regulate stress, though this has not yet been shown at the physiological level. In this study, we tested relations between maternal mindfulness in parenting and both mothers' and their infants' hypothalamic-pituitary-adrenal (HPA) axis activity…

Dysfunction of hypothalamic-hypophysial axis after traumatic brain injury in adults.

PubMed

Krahulik, David; Zapletalova, Jirina; Frysak, Zdenek; Vaverka, Miroslav

2010-09-01

Traumatic brain injury (TBI) is a major cause of serious morbidity and mortality. The incidence is 100-500/100,000 inhabitants/year. Chronic pituitary dysfunction is increasingly recognized after TBI. To define the incidence of endocrine dysfunction and risk factors, the authors describe a prospectively assessed group of patients in whom they documented hormonal functions, early diagnosis, and treatment of neuroendocrine dysfunction after TBI. Patients aged 18-65 years were prospectively observed from the time of injury to 1 year postinjury; the Glasgow Coma Scale score ranged from 3 to 14. Patients underwent evaluation of hormonal function at the time of injury and at 3, 6, and 12 months postinjury. Magnetic resonance imaging was also conducted at 1 year postinjury. During the study period, 89 patients were observed. The mean age of the patients was 36 years, there were 23 women, and the median Glasgow Coma Scale score was 7. Nineteen patients (21%) had primary hormonal dysfunction. Major deficits included growth hormone dysfunction, hypogonadism, and diabetes insipidus. Patients in whom the deficiency was major had a worse Glasgow Outcome Scale score, and MR imaging demonstrated empty sella syndrome more often than in patients without a deficit. To the authors' knowledge, this is the third largest study of its kind worldwide. The incidence of chronic hypopituitarism after TBI was higher than the authors expected. After TBI, patients are usually observed on the neurological and rehabilitative wards, and endocrine dysfunction can be overlooked. This dysfunction can be life threatening and other clinical symptoms can worsen the neurological deficit, extend the duration of physiotherapy, and lead to mental illness. The authors recommend routine pituitary hormone testing after moderate or severe TBI within 6 months and 1 year of injury.

Management of female infertility from hormonal causes.

PubMed

Luciano, Antony A; Lanzone, Antonio; Goverde, Angelique J

2013-12-01

Hormonal causes of female infertility involve ovulatory dysfunctions that may result from dysfunction of the hypothalamic-pituitary-ovarian axis, peripheral endocrine glands, nonendocrine organs, or metabolic disorders. It is important to think of anovulation not as a diagnosis but as a symptom of a metabolic or endocrine disorder that requires a thorough diagnostic evaluation to identify the specific cause and to implement effective therapies that assure the best possible pregnancy outcome and avoid long-term adverse health consequences. In most instances, the medical history points to the underlying dysfunction, which can usually be confirmed with laboratory or imaging tests. For more challenging cases, more extensive evaluations may be needed, including perturbation studies. Nevertheless, the management of anovulatory infertility is gratifying because its causes are often manifest and the treatment usually results in resumption of ovulatory cycles, restoration of fertility, and healthy offspring through natural conception without requiring expensive and intrusive assisted reproductive technologies. © 2013.

Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

PubMed

Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

2010-06-27

The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

Effects of Parental Depressive Symptoms on Child Adjustment Moderated by Hypothalamic Pituitary Adrenal Activity: Within- and between-Family Risk

ERIC Educational Resources Information Center

Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

2013-01-01

Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ("n" = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA…

Cardiovascular disease risk factors in adolescents: do negative emotions and hypothalamic-pituitary-adrenal axis function play a role?

PubMed

Pajer, Kathleen A

2007-10-01

Negative emotions such as depression and hostility/anger are important risk factors for cardiovascular disease in adults, but are often neglected in treatment or prevention programs. Adolescence is a stage of life when negative emotions often first become problematic and is also a time when the pathogenesis of cardiovascular disease appears to accelerate. The literature on negative emotions and cardiovascular disease risk factors in adolescents is reviewed here. Research indicates that negative emotions are associated with cardiovascular disease risk factors in adolescence. Negative emotions are also associated with several types of hypothalamic-pituitary-adrenal axis dysregulation. Such dysregulation appears to have a facilitatory effect on cardiovascular disease development and progression in adults. Thus, it is possible that negative emotions in adolescents may be risk factors for the development of cardiovascular disease via dysregulation of the hypothalamic-pituitary-adrenal axis. Although this hypothesis has not been directly tested, some studies indirectly support the hypothesis. Negative emotions are associated with cardiovascular disease risk factors in adolescents; it is possible that hypothalamic-pituitary-adrenal axis dysregulation is an important mechanism. This hypothesis merits further research. If the hypothesis is valid, it has significant implications for early prevention of cardiovascular disease.

Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea.

PubMed

Vimalesvaran, S; Narayanaswamy, S; Yang, L; Prague, J K; Buckley, A; Miras, A D; Franks, S; Meeran, K; Dhillo, W S

2017-01-01

Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.

Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells

PubMed Central

Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

2016-01-01

Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life.

PubMed

Vaiani, Elisa; Herzovich, Viviana; Chaler, Eduardo; Chertkoff, Lilien; Rivarola, Marco A; Torrado, Maria; Belgorosky, Alicia

2010-10-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development. © 2010 Blackwell Publishing Ltd.

Adipsic diabetes insipidus and venous thromboembolism (VTE): recommendations for addressing its hypercoagulability.

PubMed

Miljic, Dragana; Miljic, Predrag; Doknic, Mirjana; Pekic, Sandra; Stojanovic, Marko; Petakov, Milan; Popovic, Vera

2014-01-01

Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.

Sex Differences in Circadian Timing Systems: Implications for Disease

PubMed Central

Bailey, Matthew; Silver, Rae

2014-01-01

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamicadrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions. PMID:24287074

Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

ERIC Educational Resources Information Center

Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

2016-01-01

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis.

PubMed

O'Reilly, M W; Sexton, D J; Dennedy, M C; Counihan, T J; Finucane, F M; O'Brien, T; O'Regan, A W

2015-08-01

Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months. A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI. Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNF-α therapy (infliximab) after multidisciplinary team consultation. Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transcriptome-Wide Identification of Preferentially Expressed Genes in the Hypothalamus and Pituitary Gland

PubMed Central

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2012-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12–15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland. PMID:22649398

Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

PubMed

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2011-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

PubMed Central

O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

2015-01-01

Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

PubMed

Fliers, E; Boelen, A; van Trotsenburg, A S P

2014-01-01

The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

A Novel Dwarfism with Gonadal Dysfunction Due to Loss-of-Function Allele of the Collagen Receptor Gene, Ddr2, in the Mouse

PubMed Central

Kano, Kiyoshi; Marín de Evsikova, C.; Young, James; Wnek, Christopher; Maddatu, Terry P.; Nishina, Patsy M.; Naggert, Jürgen K.

2008-01-01

Smallie (slie), a spontaneous, autosomal-recessive mutation causes dwarfing and infertility in mice. The purpose of this study was to determine and characterize the underlying molecular genetic basis for its phenotype. The slie locus was mapped to chromosome 1, and fine-structure mapping narrowed the slie allele within 2 Mb between genetic markers D1Mit36 and Mpz. To pinpoint the underlying mutation quantitative real-time PCR was used to measure the relative expression levels for the genes residing within this region. Expression of one gene, Ddr2, which encodes discoidin domain receptor 2 (DDR2), was absent in slie homozygote mice. Genomic sequencing analysis detected a 150-kb deletion that extended into the Ddr2 gene transcript. Detailed phenotype analysis revealed that gonadal dysregulation underlies infertility in slie mice because all females were anovulatory and most adult males lacked spermatogenesis. The pituitary gland of prepubertal slie mice was smaller than in wild-type mice. The basal levels and gene expression for pituitary and hypothalamic hormones, and gene expression for hypothalamic-releasing hormones, were not significantly different between slie and wild-type mice. Circulating levels of IGF-1 did not differ in slie mice despite lower Igf-1 mRNA expression in the liver. After exogenous gonadotropin administration, the levels of secreted steroid hormones in both male and female adult slie mice were blunted compared to adult wild-type, but was similar to prepubertal wild-type mice. Taken together, our results indicate that the absence of DDR2 leads to growth retardation and gonadal dysfunction due to peripheral defects in hormonal-responsive pathways in slie mice. PMID:18483174

Endocannabinoids and the Endocrine System in Health and Disease.

PubMed

Hillard, Cecilia J

2015-01-01

Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.

Reversible Hypopituitarism Associated with Intravascular Large B-Cell Lymphoma: Case Report of Successful Immunochemotherapy.

PubMed

Sawada, Yusuke; Ishii, Sumiyasu; Koga, Yasuhiko; Tomizawa, Taku; Matsui, Ayako; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Shimizu, Hiroaki; Hirato, Junko; Yamada, Masanobu

2016-03-01

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. There have been only a limited number of reports regarding pituitary dysfunction associated with IVLBCL. We present a 71-year-old woman with hypopituitarism without any hypothalamic/pituitary abnormalities as assessed by magnetic resonance imaging. She presented with edema, abducens palsy, and elevated levels of lactate dehydrogenase and soluble interleukin-2 receptor. Provocative testing showed that the peaks of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and adrenocorticotropic hormone were evoked to normal levels by simultaneous administration of luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone, but the responses of these four pituitary hormones showed a delayed pattern. She was diagnosed with IVLBCL with cerebrospinal invasion by pathological findings of the bone marrow, skin, and cerebrospinal fluid. She achieved hematological remission after immunochemotherapy. Pituitary function was also restored without hormonal replacement, and the improvement of the pituitary function was confirmed by dynamic testing. We reviewed the literature with respect to hypopituitarism associated with IVLBCL. There were less than 20 case reports and most of the patients died. Endocrinological course was described in only two cases, and both of them required hormonal supplementation. To our knowledge, this is the first case of hypopituitarism induced by IVLBCL that was successfully managed by immunochemotherapy alone. This case suggests that early diagnosis and treatment of IVLBCL might improve anterior pituitary function and enable patients to avoid hormone replacement therapy.

Radiotherapy-induced hypopituitarism: a review.

PubMed

Sathyapalan, Thozhukat; Dixit, Sanjay

2012-05-01

Hypopituitarism is a disorder caused by impaired hormonal secretions from the hypothalamic-pituitary axis. Radiotherapy is the most common cause of iatrogenic hypopituitarism. The hypothalamic-pituitary axis inadvertently gets irradiated in patients receiving prophylactic cranial radiotherapy for leukemia, total body irradiation and radiotherapy for intracranial, base skull, sinonasal and nasopharyngeal tumors. Radiation-induced hypopituitarism (RIH) is insidious, progressive and largely nonreversible. Mostly, RIH involves one hypothalamic-pituitary axis; however, multiple hormonal axes deficiency starts developing at higher doses. Although the clinical effects of the hypopituitarism are more profound in children and young adults, its implications in older adults are being increasingly recognized. The risk continues to persist or increase up to 10 years following radiation exposure. The clinical management of hypopituitarism is challenging both for the patients and healthcare providers. Here we have reviewed the scale of the problem, the risk factors and the management of RIH.

Effects of halothane and methoxyflurane on the hypothalamic-pituitary-adrenal axis in rat.

PubMed

Karuri, A R; Engelking, L R; Kumar, M S

1998-10-01

Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague-Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated. Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment's time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic. Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

PubMed

Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

2005-07-01

Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased.

Amenorrhoea and reversible infertility due to obstructive hydrocephalus: literature review and case report.

PubMed

Hamilton, Kimberly; Iskandar, Bermans

2018-02-12

Endocrine abnormalities are well-recognized consequences of intracranial pathology such as pituitary tumours. Less commonly, hydrocephalus may lead to dysfunction of the endocrine system, presenting as amenorrhoea or precocious puberty. We present a case report and literature review of hydrocephalus causing endocrine abnormalities including reversible infertility. A 34 year-old female presented with amenorrhoea and infertility. MRI showed a third ventricular mass and hydrocephalus. The amenorrhoea resolved within weeks of endoscopic third ventriculostomy and tumour biopsy; pregnancy ensued within 6 months. Thirty-two cases of hydrocephalus-related amenorrhoea were reported between 1915 and 2007. All patients who underwent modern hydrocephalus treatment experienced partial or complete resolution of endocrine dysfunction. Successful pregnancy was reported in three patients, as in our case presentation. While mechanisms of dysfunction have not been completely elucidated, studies point toward loss of GnRH pulsatility due to compression of the medio-basal hypothalamic structures. Hydrocephalus can cause endocrine dysfunction, including amenorrhoea, which may reverse with CSF diversion. Therefore, cranial imaging is an important component in the evaluation of such endocrine abnormalities.

Early effects of cranial irradiation on hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic-pituitary-thyroid axis in zebrafish embryos-larvae.

PubMed

Liang, Yan-Qiu; Huang, Guo-Yong; Ying, Guang-Guo; Liu, Shuang-Shuang; Jiang, Yu-Xia; Liu, Shan

2015-01-01

The aim of this study was to investigate the effects of progestins on the hypothalamic-pituitary-thyroid (HPT) axis in the early stage of zebrafish. Zebrafish embryos were exposed to progesterone (P4) or norgestrel (NGT) at 5, 50 and 100 ng L(-1) for 144 h post fertilization (hpf), and the transcriptional levels of target genes along the hypothalamic-pituitary-thyroid axis were determined daily. The results showed that P4 had only minor effects on the mRNA expression of thyroglobulin (Tg), iodothyronine deiodinase type Ι (Dio1) and thyroid hormone receptor β (Thrb) genes. Similarly, the effects of NGT on transcripts of thyrotropin-releasing hormone (Trh), Dio1, iodothyronine deiodinase type II (Dio2) and thyroid hormone receptor α (Thra) genes were generally low. In addition, NGT resulted in some alterations of Tg and Thrb transcripts at different time points. However, a strong induction of Nis mRNA by P4 and NGT was observed in zebrafish embryos-larvae. The overall results showed that besides Nis no effects on the hypothalamic-pituitary-thyroid (HPT) axis are observed following exposure to P4 and NGT, which imply that both P4 and NGT have potential effects on the thyroid endocrine system by inducing transcript of Nis gene during the early stage of zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

Leptin is an effective treatment for hypothalamic amenorrhea

PubMed Central

Chou, Sharon H.; Chamberland, John P.; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T.; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S.

2011-01-01

Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA. PMID:21464293

Leptin is an effective treatment for hypothalamic amenorrhea.

PubMed

Chou, Sharon H; Chamberland, John P; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S

2011-04-19

Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

Administration of arginine plus growth hormone releasing hormone to evaluate growth hormone (GH) secretory status in children with GH deficiency.

PubMed

Keller, A; Donaubauer, J; Kratzsch, J; Pfaeffle, R; Hirsch, W; Kiess, W; Keller, E

2007-12-01

Diagnosis of growth hormone deficiency (GHD) in childhood is usually based on growth hormone (GH) response to at least two provocative stimuli. The aim of this study was to determine whether sequential administration of arginine (Arg) plus GH releasing hormone (GHRH) could be a useful tool in evaluating GHD in children. Thirty patients with short stature (mean age 9.0 years) with decreased growth rate were tested for GHD with Arg and the insulin tolerance test (ITT). Patients with confirmed GHD (peak GH <8 ng/ml) were subsequently tested with Arg + GHRH. Maximum GH stimulation for Arg and ITT was 6.3 (1.0-7.8) and 6.7 (0.5-7.7) ng/ml, respectively. Peak GH for the Arg + GHRH test was 36.3 (4.3-84.5) ng/ml and significantly different from the other provocative tests. Peak GH values for the three tests were not significantly correlated between tests or with clinical parameters. There were no significant differences in Arg + GHRH results between children with or without abnormal hypothalamic-pituitary MRI scans. Arg + GHRH gave higher GH levels than insulin or Arg alone. Because of the different causes of childhood GHD (hypothalamic and/or pituitary dysfunction), the Arg + GHRH test is unsuitable .for evaluating GHD and deciding whether GH replacement therapy is indicated.

Prevention of reflex natriuresis after acute unilateral nephrectomy by neonatal administration of MSG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, S.Y.; Wiedemann, E.; Deschepper, C.F.

1987-02-01

Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. The authors measured plasma immunoreactive NTF-like material (IR-NTF) by radioimmunoassay, before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increasedmore » from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN as sodium excretion (U/sub Na/V) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration, nor did U/sub Na/V increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natruiuresis after AUN, and therefore lend further support to the concept of a casual relationship between these two consequences of AUN.« less

Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion

PubMed Central

McKlveen, Jessica M.; Myers, Brent; Flak, Jonathan N.; Bundzikova, Jana; Solomon, Matia B.; Seroogy, Kim B.; Herman, James P.

2013-01-01

Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation. PMID:23683655

Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

ERIC Educational Resources Information Center

Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

2011-01-01

Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

Diffuse traumatic brain injury affects chronic corticosterone function in the rat

PubMed Central

Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan

2016-01-01

As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

Bone metabolism in anorexia nervosa and hypothalamic amenorrhea.

PubMed

Chou, Sharon H; Mantzoros, Christos

2018-03-01

Anorexia nervosa (AN) and hypothalamic amenorrhea (HA) are states of chronic energy deprivation associated with severely compromised bone health. Poor bone accrual during adolescence followed by increased bone loss results in lifelong low bone density, degraded bone architecture, and higher risk of fractures, despite recovery from AN/HA. Amenorrhea is only one of several compensatory responses to the negative energy balance. Other hypothalamic-pituitary hormones are affected and contribute to bone deficits, including activation of hypothalamic-pituitary-adrenal axis and growth hormone resistance. Adipokines, particularly leptin, provide information on fat/energy stores, and gut hormones play a role in the regulation of appetite and food intake. Alterations in all these hormones influence bone metabolism. Restricted in scope, current pharmacologic approaches to improve bone health have had overall limited success. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

PubMed

Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali

2018-02-17

Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders.

PubMed

Contoreggi, Carlo; Rice, Kenner C; Chrousos, George

2004-01-01

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.

Pituitary disorders as a predictor of apathy and executive dysfunction in adult survivors of childhood brain tumors.

PubMed

Fox, Michelle E; King, Tricia Z

2016-11-01

The relationship between apathy and endocrine dysfunction, both frequent outcomes of neurological insult, has not yet been investigated in brain tumor survivors. The present study aimed to assess the relationship between pituitary disorders and apathy and other facets of executive function in long-term adult survivors of childhood brain tumors and to differentiate between apathy and depression in this population. Seventy-six adult survivors of childhood brain tumors at least 5 years past diagnosis participated. An informant completed the Frontal Systems Behavior Scale (FrSBe), and 75 of the 76 participants completed a Structured Clinical Interview for the DSM-IV-TR (SCID). Information on neuroendocrine dysfunction was obtained through medical chart review. Clinically significant levels of apathy on the FrSBe were identified in 41% of survivors. Pituitary dysfunction significantly explained 9% of the variance in apathy scores and affected whether an individual presented with clinical levels of apathy. Pituitary dysfunction predicted higher levels of executive dysfunction but did not impact whether a participant reached clinical levels of executive dysfunction. A past major depressive episode (MDE) significantly predicted current apathy but showed no relationship with pituitary disorders. Radiation treatment predicted pituitary dysfunction but not the differences in apathy or executive functions. Apathy and executive dysfunction in survivors of childhood brain tumors are strongly predicted by pituitary dysfunction, and individuals with pituitary dysfunction are more likely to present with clinical levels of apathy as adults. Clinical levels of apathy may present absent of current depression, and pituitary dysfunction impacts apathy uniquely. © 2016 Wiley Periodicals, Inc.

Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

PubMed

Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H

2017-10-03

Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

The Hypothalamic-Pituitary-Adrenal Axis and Anesthetics: A Review.

PubMed

Besnier, Emmanuel; Clavier, Thomas; Compere, Vincent

2017-04-01

The hypothalamic-pituitary-adrenal (HPA) axis is essential for human adaptation to stress. However, many anesthetic agents may interfere with the activity of this axis. Although etomidate is known for its suppressive effect on HPA axis function, in vitro evidence suggests that many other drugs used in anesthesia care may also interfere with HPA activity. In this review, we discuss the mechanisms by which all HPA axis activity may be altered during anesthesia and critical care and focus on the impact of hypnotic and analgesic drugs.

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

PubMed

Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

2009-04-14

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

Thyroid abnormalities after therapeutic external radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, S.L.; McDougall, I.R.; Constine, L.S.

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benignmore » adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.« less

ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility

PubMed Central

Bliss, Stuart P.; Miller, Andrew; Navratil, Amy M.; Xie, JianJun; McDonough, Sean P.; Fisher, Patricia J.; Landreth, Gary E.; Roberson, Mark S.

2009-01-01

Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHβ expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. PMID:19372235

Pituitary size in patients with Laron syndrome (primary GH insensitivity).

PubMed

Kornreich, Liora; Horev, Gadi; Schwarz, Michael; Karmazyn, Boaz; Laron, Zvi

2003-03-01

The purpose of the present study was to investigate whether lifelong secretion of high levels of GH, characteristic of Laron syndrome, leads to an increase in the size of the pituitary gland. Eleven patients (six females, five males) with Laron syndrome underwent magnetic resonance imaging of the pituitary region with a system operating at 0.5 T. There were nine adults aged 36-68 Years and two children, a 4-Year-old boy and a 9-Year-old girl. The latter patient had been treated with IGF-I (150-180 mg/kg per day) since the age of 3 Years; all the other patients were untreated. The height of the adenohypophysis was measured on the sagittal images and compared with reference values for age and sex. The height of the adenohypophysis was within the normal range for age and gender in all patients, except for one male, who had a small gland. No congenital anomalies of the pituitary-hypothalamic region were detected. Despite the lifelong high levels of GH, no pituitary hypertrophy was detected. The anatomy of the pituitary-hypothalamic region in Laron syndrome is normal.

Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without gadolinium in pituitary diseases.

PubMed

Godano, Elisabetta; Morana, Giovanni; Di Iorgi, Natascia; Pistorio, Angela; Allegri, Anna Elsa Maria; Napoli, Flavia; Gastaldi, Roberto; Calcagno, Annalisa; Patti, Giuseppa; Gallizia, Annalisa; Notarnicola, Sara; Giaccardi, Marta; Noli, Serena; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Maghnie, Mohamad

2018-06-01

To investigate the role of T2-DRIVE MRI sequence in the accurate measurement of pituitary stalk (PS) size and the identification of PS abnormalities in patients with hypothalamic-pituitary disorders without the use of gadolinium. This was a retrospective study conducted on 242 patients who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135 eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33 showed 'ectopic' PP (EPP). Two readers independently measured the size of PS in patients with eutopic PP at the proximal, midpoint and distal levels on pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length, height, width and volume of the anterior pituitary (AP), PP height and length and PP area were analyzed. Significant agreement between the two readers was obtained for T2-DRIVE PS measurements in patients with 'eutopic' PP; a significant difference was demonstrated between the intraclass correlation coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7% compared to 30.3% of T1 pre-contrast sequences. A significant association was found between the visibility of PS on T2-DRIVE and the height of AP. T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size and the recognition of PS abnormalities; the use of gadolinium-based contrast media does not add significant information and may thus be avoided. © 2018 European Society of Endocrinology.

Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study.

PubMed

Lavrnja, Irena; Trifunovic, Svetlana; Ajdzanovic, Vladimir; Pekovic, Sanja; Bjelobaba, Ivana; Stojiljkovic, Mirjana; Milosevic, Verica

2014-02-10

Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process. Copyright © 2013 Elsevier Inc. All rights reserved.

Co-Morbidity of PTSD and Immune System Dysfunction: Opportunities for Treatment

PubMed Central

Neigh, Gretchen N.; Ali, Fariya F.

2016-01-01

Posttraumatic stress disorder (PTSD) is defined as a psychiatric disorder; however, PTSD co-occurs with multiple somatic manifestations. People living with PTSD commonly manifest dysregulations in the systems that regulate the stress response, including the hypothalamic-pituitary-adrenal (HPA) axis, and development of a pro-inflammatory state. Additionally, somatic autoimmune and inflammatory diseases and disorders have a high rate of co-morbidity with PTSD. Recognition and understanding of the compounding effect that these disease states can have on each other, evidenced from poorer treatment outcomes and accelerated disease progression in patients suffering from co-morbid PTSD and/or other autoimmune and inflammatory diseases, has the potential to lead to additional treatment opportunities. PMID:27479489

Ageing Holocaust survivors in Australia.

PubMed

Paratz, Elizabeth D; Katz, Benny

2011-02-21

In recent years, a phenomenon of "late effects of the Holocaust" has emerged, with impacts on the psychological and physical health of ageing Holocaust survivors. As Holocaust survivors age, they may experience heightened anxiety around normal processes of ageing, worsened post-traumatic stress disorder with cognitive decline, and fear of the medical system. Holocaust survivors are at increased risk of osteoporosis, cardiometabolic disease due to hypothalamic-pituitary-adrenal axis dysfunction, cancer, and sequelae of Nazi medical experiments. From existing medical literature on this topic, practical principles of management are derived to create a framework for sensitive medical management of Holocaust survivors in Australia. The issues discussed are also relevant to the wider geriatric refugee or prisoner-of-war experience.

Incidence of late endocrine dysfunction following irradiation for childhood medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abayomi, O.K.; Sadeghi-Nejad, A.

1986-06-01

A retrospective analysis of treatment in 20 patients who had received post-operative radiotherapy for medulloblastoma between 1969 and 1977 was completed. The patients were followed for a minimum of 60 months. Eleven patients survived for 5 or more years after treatment. The patients received 3600 cGy to the whole brain. The posterior fossa received 5600 cGY and the spinal axis 3600 cGY. Eight of eleven patients developed growth impairment; 6 of 7 patients had growth hormone deficiency. Since all endocrine gland failures are amenable to therapy, early attention to patients' growth rate and detection of hypothalamic-pituitary failure, would be ofmore » benefit to longterm survivors.« less

Survival and growth in a woman with untreated hypothalamic panhypopituitarism of 21 years' duration.

PubMed

Tolis, G; Cruess, S; Goldstein, M; Friesen, H G; Rochefort, J G

1974-09-21

A 29-year-old woman with evidence of a craniopharyngioma and documented panhypopituitarism is described. Clinical and laboratory evaluation revealed deficiencies of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone and antidiuretic hormone. Prompt release of several pituitary hormones was noticed after administration of the hypothalamic releasing hormones FSH/LH-RF and thyrotropin-releasing hormone, whereas insulin-induced hypoglycemia, levodopa, chlorpromazine and clomiphene citrate, all of which act at the level of the hypothalamus, did not alter basal pituitary secretion. The patient's height of 60 inches, despite panhypopituitarism, and the interpretation of the above data are discussed in the light of current concepts regarding the dynamics of the hypothalamic-hypophyseal system.

Survival and growth in a woman with untreated hypothalamic panhypopituitarism of 21 years' duration

PubMed Central

Tolis, G.; Cruess, S.; Goldstein, M.; Friesen, H. G.; Rochefort, J. G.

1974-01-01

A 29-year-old woman with evidence of a craniopharyngioma and documented panhypopituitarism is described. Clinical and laboratory evaluation revealed deficiencies of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone and antidiuretic hormone. Prompt release of several pituitary hormones was noticed after administration of the hypothalamic releasing hormones FSH/LH-RF and thyrotropin-releasing hormone, whereas insulin-induced hypoglycemia, levodopa, chlorpromazine and clomiphene citrate, all of which act at the level of the hypothalamus, did not alter basal pituitary secretion. The patient's height of 60 inches, despite panhypopituitarism, and the interpretation of the above data are discussed in the light of current concepts regarding the dynamics of the hypothalamic-hypophyseal system. ImagesFIG. 1 PMID:4370418

Pathology of excessive production of growth hormone.

PubMed

Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

1986-08-01

Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'.

Chapter 11.18 - Neuroendocrine Control of Female Reproduction.

EPA Science Inventory

The hypothalamus and pituitary are known to play roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently the endocrine control of ...

Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning.

PubMed

Ogawa, Yoshikazu; Niizuma, Kuniyasu; Tominaga, Teiji

2017-11-01

Craniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions. This retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated. Gross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of anti-diuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p=0.016). Pituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life could be possible to preserve the lateral wall of the third ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

PubMed

Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

2015-01-01

Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

Protective effects of Lycium barbarum polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice.

PubMed

Shi, Guang-Jiang; Zheng, Jie; Wu, Jing; Qiao, Hai-Qi; Chang, Qing; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

2017-09-30

Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen's testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study.

PubMed

McBeth, J; Silman, A J; Gupta, A; Chiu, Y H; Ray, D; Morriss, R; Dickens, C; King, Y; Macfarlane, G J

2007-01-01

To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal (HPA) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain (CWP). We conducted a population-based prospective cohort study. Current pain and psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile, 463 were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis function. Diurnal function was measured by assessing levels of salivary cortisol in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and a potentially stressful clinical examination. All subjects were followed up 15 months later to identify cases of new-onset CWP. A total of 241 subjects (94.9%) completed the followup study, and 28 (11.6%) reported the new onset of CWP. High levels of cortisol post-dexamethasone (odds ratio [OR] 3.53, 95% confidence interval [95% CI] 1.17-10.65), low levels in morning saliva (OR 1.43, 95% CI 0.52-3.94), and high levels in evening saliva (OR 2.32, 95% CI 0.64-8.42) were all associated with CWP. These 3 factors were found to be independent and additive predictors of CWP (OR for all 3 factors 8.5, 95% CI 1.5-47.9) in analyses controlling for age, sex, depression, sleep disturbance, recent traumatic life events, and pain status. One or more of these 3 HPA factors identified 26 (92.9%) cases of new-onset CWP. Among a group of psychologically at-risk subjects, dysfunction of the HPA axis helps to distinguish those who will and will not develop new-onset CWP.

Flatfish metamorphosis: a hypothalamic independent process?

PubMed

Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

2015-03-15

Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Psychopathological traits of adolescents with functional hypothalamic amenorrhea: a comparison with anorexia nervosa.

PubMed

Bomba, Monica; Corbetta, Fabiola; Bonini, Luisa; Gambera, Alessandro; Tremolizzo, Lucio; Neri, Francesca; Nacinovich, Renata

2014-03-01

Functional hypothalamic amenorrhea (FHA) is a form of anovulation, due to the suppression of hypothalamic-pituitary-ovarian axis, not related to identifiable organic causes. Like adolescents with anorexia nervosa (AN), subjects with FHA show dysfunctional attitudes, low self-esteem, depressive mood, anxiety and inability to cope with daily stress. The aim of the study is to examine similarities and differences between FHA and AN in terms of clinical profiles and psychological variables. 21 adolescents with FHA, 21 adolescents with anorexia nervosa, and 21 healthy adolescents were included in the study. All the teenagers completed a battery of self-administered psychological tests for the detection of behaviors and symptoms attributable to the presence of an eating disorder (EDI-2), depression (CDI), and alexithymia (TAS-20). Different from healthy controls, subjects with FHA and with AN shared common psychopathological aspects, such as maturity issues, social insecurity and introversion, a tendency to depression, excessive concerns with dieting, and fear of gaining weight. Nevertheless, adolescents with AN presented a more profound psychopathological disorder as observed at test comparisons with subjects with FHA. Results show a clinical spectrum that includes AN and FHA and suggest the necessity to treat FHA with a multidisciplinary approach for both organic and psychological aspects.

Prolonged hypothalamic-pituitary-adrenal axis activation after acute coronary syndrome in the GENESIS-PRAXY cohort.

PubMed

Tang, Andrew R; Rabi, Doreen M; Lavoie, Kim L; Bacon, Simon L; Pilote, Louise; Kline, Gregory A

2018-01-01

Background Glucocorticoid excess has been linked with cardiovascular disease. Little is known about the long-term cortisol response in patients after acute coronary syndrome. Design The objective of this study was to describe the distribution of salivary cortisol in the post-acute phase of acute coronary syndrome and to describe the association of late-night salivary cortisol with cardiovascular risk factors. Methods We used late-night salivary cortisol measurements post-discharge to estimate hypothalamic-pituitary-adrenal axis activity in 309 patients aged 18-55 years enrolled in the GENESIS-PRAXY study from January 2009-April 2013. We evaluated hypothalamic-pituitary-adrenal axis activity and its association with hypertension, dyslipidemia, diabetes, smoking, family history, prior acute coronary syndrome, psychiatric diseases, acute coronary syndrome severity, as well as mortality and rate of rehospitalization at 12 months. Results Persistently elevated late-night salivary cortisol>2.92 nmol/l was seen in 99 (32.0%) patients: within the range of what may be seen in Cushing's disease. Elevated late-night salivary cortisol was associated with previous acute coronary syndrome (13.3% vs 24.2%, p = 0.02), peripheral vascular disease (3.8% vs 13.1%, p = 0.002), and smoking (32.9% vs 46.5% p = 0.02). Elevated late-night salivary cortisol was associated with higher hemoglobin A1c values (5.6 ± 3.0 vs 6.1 ± 2.9, p = 0.008) and lower high density lipoprotein values (0.94 ± 0.53 vs 0.86 ± 0.50, p = 0.01). There were no differences in psychiatric symptom scores, acute coronary syndrome severity or mortality, and rate of rehospitalization at 12 months. Conclusions Many patients post-acute coronary syndrome have prolonged, marked activation of the hypothalamic-pituitary-adrenal axis. Late-night salivary cortisol co-associates with several cardiovascular risk factors. Further studies are needed to confirm the exact role of hypothalamic-pituitary-adrenal axis activity in the pathophysiology of cardiovascular disease.

Clinical prevalence and outcome impact of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a systematic review with meta-analysis.

PubMed

Robba, Chiara; Bacigaluppi, Susanna; Bragazzi, Nicola; Lavinio, Andrea; Gurnell, Mark; Bilotta, Federico; Menon, David K

2016-10-01

Pituitary dysfunction is reported to be a common complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this meta-analysis is to analyze the literature on clinical prevalence, risk factors and outcome impact of pituitary dysfunction after aSAH, and to assess the possible need for pituitary screening in aSAH patients. We performed a systematic review with meta-analysis based on a comprehensive search of four databases (PubMed/MEDLINE, ISI/Web of Science, Scopus and Google Scholar). A total of 20 papers met criteria for inclusion. The prevalence of pituitary dysfunction in the acute phase (within the first 6 months after aSAH) was 49.30 % (95 % CI 41.6-56.9), decreasing in the chronic phase (after 6 months from aSAH) to 25.6 % (95 % CI 18.0-35.1). Abnormalities in basal hormonal levels were more frequent when compared to induction tests, and the prevalence of a single pituitary hormone dysregulation was more frequent than multiple pituitary hormone dysregulation. Increasing age was associated with a lower prevalence of endocrine dysfunction in the acute phase, and surgical treatment of the aneurysm (clipping) was related to a higher prevalence of single hormone dysfunction. The prevalence of pituitary dysfunction did not correlate with the outcome of the patient. Neuroendocrine dysfunction is common after aSAH, but these abnormalities have not been shown to consistently impact outcome in the data available. There is a need for well-designed prospective studies to more precisely assess the incidence, clinical course, and outcome impact of pituitary dysfunction after aSAH.

Identification of differentially expressed genes in the zebrafish hypothalamus - pituitary axis

PubMed Central

Toro, Sabrina; Wegner, Jeremy; Muller, Marc; Westerfield, Monte; Varga, Zoltan M.

2009-01-01

The vertebrate hypothalamic-pituitary axis (HP) is the main link between the central nervous system and endocrine system. Although several signal pathways and regulatory genes have been implicated in adenohypophysis ontogenesis, little is known about hypothalamic and neurohypophysial development or when the HP matures and becomes functional. To identify markers of the HP, we constructed subtractive cDNA libraries between adult zebrafish hypothalamus and pituitary. We identified previously published genes and ESTs and novel zebrafish genes, some of which were predicted by genomic database analysis. We also analyzed expression patterns of these genes and found that several are expressed in the embryonic and larval hypothalamus, neurohypophysis, and/or adenohypophysis. Expression at these stages makes these genes useful markers to study HP maturation and function. PMID:19166982

Effects of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction

EPA Science Inventory

The hypothalamus and pituitary are known to play key roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently, the endocrine contro...

Granular cell tumour of the neurohypophysis: an unusual cause of hypopituitarism.

PubMed

Bello, Carlos Tavares; Cipriano, Patricia; Henriques, Vanessa; Duarte, João Sequeira; Marques, Conceição Canas

2018-01-01

Granular cell tumours (GCT) are rare, slow-growing, benign neoplasms that are usually located in the head and neck. They are more frequent in the female gender and typically have an asymptomatic clinical course, being diagnosed only at autopsy. Symptomatic GCT of the neurohypophysis are exceedingly rare, being less than 70 cases described so far. The authors report on a case of a 28-year-old male that presented to the Endocrinology clinic with clinical and biochemical evidence of hypogonadism. He also reported minor headaches without any major visual symptoms. Further laboratory tests confirmed hypopituitarism (hypogonadotrophic hypogonadism, central hypothyroidism and hypocortisolism) and central nervous system imaging revealed a pituitary macroadenoma. The patient underwent transcranial pituitary adenoma resection and the pathology report described a GCT of the neurohypophysis with low mitotic index. The reported case is noteworthy for the rarity of the clinicopathological entity. Symptomatic GCTs are rare CNS tumours whose cell of origin is not well defined that usually give rise to visual symptoms, headache and endocrine dysfunction.Imaging is quite unspecific and diagnosis is difficult to establish preoperatively.Surgical excision is challenging due to lesion's high vascularity and propensity to adhere to adjacent structures.The reported case is noteworthy for the rarity of the clinicopathological entity.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

PubMed

Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

PubMed Central

Dietrich, Johannes W.; Landgrafe, Gabi; Fotiadou, Elisavet H.

2012-01-01

This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range. PMID:23365787

Diagnosis of hypogonadism: clinical assessments and laboratory tests.

PubMed

Carnegie, Christina

2004-01-01

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.

Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms

PubMed Central

Romanò, Nicola; Guillou, Anne; Martin, Agnès O; Mollard, Patrice

2017-01-01

Small assemblies of hypothalamic “parvocellular” neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting pituitary hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of pituitary prolactin secretion, a key reproductive hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz–10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local–global integration to connect brain–pituitary rhythms and pace hormone secretion. PMID:28193889

[Panhypopituitarism and dwarfism in a man with a primary empty sella turcica (author's transl)].

PubMed

Turpin, G; Jambart, S; de Gennes, J L

1979-03-10

Endocrine features associated with the primary empty sella turcica syndrom are rare; they are usually related to a pituitary microadenoma and more rarely to an idiopathic panhypop ituitarism. A pituitary dwarfism with an idiopathic panhypopituitarism of hypothalamic origin, associated with an "empty" sella turcica containing functional and stimulable pituitary tissue, is reported in a 27 year old male Moraccan.

A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

PubMed

Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F

2001-10-01

To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case-control study in long-term survivors from cancer in the head and neck region.

PubMed

Olsson, Erik; Eckerström, Carl; Berg, Gertrud; Borga, Magnus; Ekholm, Sven; Johannsson, Gudmundur; Ribbelin, Susanne; Starck, Göran; Wysocka, Anna; Löfdahl, Elisabet; Malmgren, Helge

2012-11-29

An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients' lowered QoL was coupled to a reduction in hippocampal volume. Patients (11 men and 4 women, age 31-65) treated for head and neck cancer 4-10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 - 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon's signed rank test were used for the main statistical analysis. There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. The study gives solid evidence against the hypothesis that the patients' lowered quality of life was due to a major reduction of hippocampal volume.

Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

PubMed

Oyola, Mario G; Handa, Robert J

2017-09-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis.

PubMed

Hillard, Cecilia J; Beatka, Margaret; Sarvaideo, Jenna

2016-12-06

The elucidation of Δ9-tetrahydrocannabinol as the active principal of Cannabis sativa in 1963 initiated a fruitful half-century of scientific discovery, culminating in the identification of the endocannabinoid signaling system, a previously unknown neuromodulatory system. A primary function of the endocannabinoid signaling system is to maintain or recover homeostasis following psychological and physiological threats. We provide a brief introduction to the endocannabinoid signaling system and its role in synaptic plasticity. The majority of the article is devoted to a summary of current knowledge regarding the role of endocannabinoid signaling as both a regulator of endocrine responses to stress and as an effector of glucocorticoid and corticotrophin-releasing hormone signaling in the brain. We summarize data demonstrating that cannabinoid receptor 1 (CB1R) signaling can both inhibit and potentiate the activation of the hypothalamic-pituitary-adrenal axis by stress. We present a hypothesis that the inhibitory arm has high endocannabinoid tone and also serves to enhance recovery to baseline following stress, while the potentiating arm is not tonically active but can be activated by exogenous agonists. We discuss recent findings that corticotropin-releasing hormone in the amygdala enables hypothalamic-pituitary-adrenal axis activation via an increase in the catabolism of the endocannabinoid N-arachidonylethanolamine. We review data supporting the hypotheses that CB1R activation is required for many glucocorticoid effects, particularly feedback inhibition of hypothalamic-pituitary-adrenal axis activation, and that glucocorticoids mobilize the endocannabinoid 2-arachidonoylglycerol. These features of endocannabinoid signaling make it a tantalizing therapeutic target for treatment of stress-related disorders but to date, this promise is largely unrealized. © 2017 American Physiological Society. Compr Physiol 7:1-15, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

PubMed Central

Córdoba-Chacón, José; Gahete, Manuel D.; Castaño, Justo P.; Kineman, Rhonda D.

2011-01-01

Somatostatin (SST) inhibits growth hormone (GH) secretion and regulates multiple processes by signaling through its receptors sst1–5. Differential expression of SST/ssts may contribute to sex-specific GH pattern and fasting-induced GH rise. To further delineate the tissue-specific roles of SST and sst1–5 in these processes, their expression patterns were evaluated in hypothalamus, pituitary, and stomach of male and female mice under fed/fasted conditions in the presence (wild type) or absence (SST-knockout) of endogenous SST. Under fed conditions, hypothalamic/stomach SST/ssts expression did not differ between sexes, whereas male pituitary expressed more SST and sst2A/2B/3/5A/5TMD2/5TMD1 and less sst1, and male pituitary cell cultures were more responsive to SST inhibitory actions on GH release compared with females. This suggests that local pituitary SST/ssts can contribute to the sexually dimorphic pattern of GH release. Fasting (48 h) reduced stomach sst2A/B and hypothalamic SST/sst2A expression in both sexes, whereas it caused a generalized downregulation of pituitary sst subtypes in male and of sst2A only in females. Thus, fasting can reduce SST sensitivity across tissues and SST input to the pituitary, thereby jointly contributing to enhance GH release. In SST-knockout mice, lack of SST differentially altered sst subtype expression levels in both sexes, supporting an important role for SST in sex-dependent control of GH axis. Evaluation of SST, IGF-I, and glucocorticoid effects on hypothalamic and pituitary cell cultures revealed that these hormones could directly account for alterations in sst2/5 expression in the physiological states examined. Taken together, these results indicate that changes in SST output and sensitivity can contribute critically to precisely define, in a tissue-dependent manner, the sex-specific metabolic regulation of the GH axis. PMID:20943754

Occurrence of pituitary dysfunction following traumatic brain injury.

PubMed

Bondanelli, Marta; De Marinis, Laura; Ambrosio, Maria Rosaria; Monesi, Marcello; Valle, Domenico; Zatelli, Maria Chiara; Fusco, Alessandra; Bianchi, Antonio; Farneti, Marco; degli Uberti, Ettore C I

2004-06-01

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

EPA Science Inventory

Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

EPA Science Inventory

A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

PubMed

Deal, Cheri; Hasselmann, Caroline; Pfäffle, Roland W; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Shavrikova, Elena P; Cutler, Gordon B; Blum, Werner F

2013-01-01

Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management. Copyright © 2013 S. Karger AG, Basel.

[Symptomatic hypersomnia due to orexin deficiency in hypothalamic lesions].

PubMed

Kanbayashi, Takashi; Arii, Junko; Kubota, Hiroaki; Yano, Tamami; Kashiwagi, Mitsuru; Yoshikawa, Sousuke; Tohyama, Jun; Sawaishi, Yukio

2006-09-01

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and other abnormal manifestations of REM sleep. Recently, it was discovered that the pathophysiology of idiopathic narcolepsy-cataplexy is linked to orexin ligand deficiency in the brain and cerebrospinal fluid. Orexin neurons localize in the posterior hypothalamic area, which was previously described as "waking center" by von Economo in 1920s. Hypersomnia due to orexin ligand deficiency can also occur during the course of other neurological conditions, such as hypothalamic tumor, encephalopathy and demyelinating disorder (i.e. symptomatic hypersomnia). We experienced 8 pediatric cases with symptomatic hypersomnia. These cases were diagnosed as brain tumor (n = 2), head trauma (n = 1), encephalopathy (n = 1), demyelinating disorder (n = 3) and infarction (n = 1). Six pediatric cases with orexin measurements from the literatures were additionally included and total 14 cases were studied. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, a review of the case histories reveals numerous unquestionable cases of symptomatic hypersomnia. In these cases, the occurrences of the hypersomnia run parallel with the rise and fall of the causative diseases. Most of symptomatic hypersomnia cases show both extended nocturnal sleep time and EDS consisting of prolonged sleep episodes of NREM sleep. The features of nocturnal sleep and EDS in symptomatic hypersomnia are more similar to idiopathic hypersomnia than to narcolepsy.

A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

PubMed

Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; Penninx, Brenda W J H; Dekker, Joost

2014-07-09

Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders

PubMed Central

2014-01-01

Background Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain. Methods Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level). Results In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response. Conclusions Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain. PMID:25007969

Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

PubMed Central

Ben-Zvi, Amos; Vernon, Suzanne D.; Broderick, Gordon

2009-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning. PMID:19165314

Hypogonadism: Its Prevalence and Diagnosis.

PubMed

Ross, Anna; Bhasin, Shalender

2016-05-01

Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Pituitary Dysfunction from an Unruptured Ophthalmic Internal Carotid Artery Aneurysm with Improved 2-year Follow-up Results: A Case Report.

PubMed

Qi, Meng; Ye, Ming; Li, Meng; Zhang, Peng

2018-01-01

Internal carotid artery (ICA) supraclinoid segment aneurysms extending into the sellar region and leading to pituitary dysfunction are a rare occurrence. To date, long-term follow up of pituitary function 2 years post-treatment has never been reported. Herein, we present a case of pituitary dysfunction due to an unruptured ophthalmic segment internal carotid artery aneurysm and report improved 2-year follow-up results. A 76-year-old male presented with disturbed consciousness due to hyponatremia, which was caused by hypoadrenocorticism resulting from pituitary dysfunction complicated by hypogonadism and hypothyroidism. Computed tomography angiography revealed an intracranial aneurysm of the ophthalmic segment of the right ICA with an intrasellar extension. Thus, digital subtraction angiography and coil embolization were performed, followed by hormone replacement therapy. A 2-year follow-up revealed a partial improvement in the pituitary function, including complete restoration of thyroid-stimulating hormone level and other thyroid hormones levels, and partial restoration of testosterone levels, followed by discontinuation of thyroid hormone replacement therapy. However, the mechanisms of such pituitary dysfunction and the effects of various treatments, including clipping and coiling, on different hormones of pituitary function recovery remain unclear. A long-term follow-up of >2 years may elucidate the pituitary function recovery post-treatment and provide a medication adjustment for hormone replacement therapy.

Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy.

PubMed

Inge, Thomas H; Pfluger, Paul; Zeller, Meg; Rose, Susan R; Burget, Lukas; Sundararajan, Sumana; Daniels, Stephen R; Tschöp, Matthias H

2007-08-01

A 14-year-old boy presented with daytime somnolence, intermittent emesis and hypothyroidism. Neuroimaging revealed a calcified suprasellar intracranial mass, suspected to be a craniopharyngioma. Subtotal resection of the tumor confirmed the diagnosis. Extreme obesity (BMI >60 kg/m(2)) and hyperinsulinemia followed tumor resection and cranial irradiation. Dietary interventions were unsuccessful, and pharmacologic intervention (i.e. octreotide) only slowed the rate of weight gain. Radiography documented the suprasellar mass. Following surgical resection and radiotherapy, hypothalamic-pituitary deficiencies were found. Preprandial and postprandial excursions of insulin, active ghrelin and leptin were measured before and after gastric bypass surgery. Panhypopituitarism, hypothalamic obesity and hyperinsulinemia following craniopharyngioma therapy. Severe caloric restriction, octreotide, and pituitary hormone replacement did not produce weight loss. Gastric bypass surgery led to reduced food cravings, significant weight loss, and amelioration of obesity-related comorbidities. Correction of fasting hyperinsulinemia, normalization of postprandial insulin responses, and reductions in active ghrelin and leptin concentrations were also observed.

Neuroendocrine Causes of Amenorrhea—An Update

PubMed Central

Fourman, Lindsay T.

2015-01-01

Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

Diet and insulinlike growth factor I in relation to body composition in women with exercise-induced hypothalamic amenorrhea.

PubMed

Crist, D M; Hill, J M

1990-06-01

To assess the potential influence of diet and endogenous peptide anabolic hormone secretion on exercise-related differences in body composition, we compared levels of macronutrient intake, insulinlike growth factor I (IGF-I), and fat-free mass (FFM) and fat mass (FM) in matched groups of exercising women with and without secondary hypothalamic amenorrhea. Women were tightly matched according to somatotype and grouped into those with exercise amenorrhea (EXam, n = 6), exercise eumennorhea (EXeu, n = 5), and sedentary eumennorheic controls (SED, n = 5). Although no between-group difference was observed in FFM, the EXeu subjects had a significantly lower fat fraction and a significantly elevated FFM/FM ratio. Kilocaloric and protein intakes did not differ between groups, but dietary fat intake was lowest and carbohydrate intake highest in the EXam subjects. Dietary macronutrients were not correlated with the FFM/FM ratio. However, levels of insulinlike growth factor I were significantly correlated to the FFM/FM ratio and there was a clear trend for the hormone to be highest in the EXeu subjects. We conclude that differences in body composition between exercising women with and without exercise-induced hypothalamic-pituitary dysfunction were related to an alteration in IGF-I secretion, although differences in macronutrient intake might also be a factor. Further studies are warranted to elaborate upon the dietary and hormonal factors regulating the body composition response to exercise.

Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader-Willi syndrome.

PubMed

Radicioni, A F; Di Giorgio, G; Grugni, G; Cuttini, M; Losacco, V; Anzuini, A; Spera, S; Marzano, C; Lenzi, A; Cappa, M; Crinò, A

2012-01-01

Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear. To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males. Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years. Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH. PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis). © 2011 Blackwell Publishing Ltd.

Feed intake of gilts following intracerebroventicular injection of the novel hypothalamic RFamide (RFa) neuropeptide, 26RFa

USDA-ARS?s Scientific Manuscript database

RFamide (RFa) peptides have been implicated in a broad spectrum of biological processes including energy expenditure and feed intake. 26RFa is a recently discovered hypothalamic neuropeptide that altered the release of pituitary hormones and stimulated feed intake via a NPY-specific mechanism in rat...

Radioimmunoassay of human homologous prolactin in serum with commercially available reagents. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kao, P.C.; Jiang, N.S.; Abboud, C.F.

A clinically useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (..mu..g/liter) as follows for serum prolactin: normal men, 8.9 +- 5.2 (mean +- SD); normal women, 11.8 +- 5.5; normal women taking contraceptive pills, 9.2 +- 5.0; pregnant women in the third trimester, 188 +- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +- 6.3; in some patients with amenorrhea and galactorrhea ofmore » diverse origin, 78.2 +- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function.« less

Functional hypothalamic amenorrhea due to increased CRH tone in melanocortin receptor 2-deficient mice.

PubMed

Matsuwaki, Takashi; Nishihara, Masugi; Sato, Tsuyoshi; Yoda, Tetsuya; Iwakura, Yoichiro; Chida, Dai

2010-11-01

Exposure to chronic stressors results in dysregulation of the hypothalamic-pituitary-adrenal axis and a disruption in reproduction. CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis induces the secretion of ACTH from the pituitary, which stimulates adrenal steroidogenesis via the specific cell-surface melanocortin 2 receptor (MC2R). Previously, we demonstrated that MC2R(-/-) mice had undetectable levels of corticosterone despite high ACTH levels. Here, we evaluated the reproductive functions of female MC2R(-/-) mice and analyzed the mechanism of the disrupted cyclicity of these mice. The expression of CRH in the paraventricular nucleus was significantly increased in MC2R(-/-) mice under nonstressed conditions. Although MC2R(-/-) females were fertile, they showed a prolonged estrous cycle. After hormonal stimulation, MC2R(-/-) females produced nearly-normal numbers of eggs, but slightly less than MC2R(+/-) females, and showed near-normal ovarian histology. During diestrus, the number of GnRH-positive cells in the medial preoptic area was significantly reduced in MC2R(-/-) females. CRH type 1 receptor antagonist restored estrous cyclicity in MC2R(-/-) females. Kisspeptin-positive areas in the arcuate nucleus were comparable, whereas kisspeptin-positive areas in the anteroventral periventricular nucleus in MC2R(-/-) females were significantly reduced compared with MC2R(+/-) females, suggesting that arcuate nucleus kisspeptin is not involved, but anteroventral periventricular nucleus kisspeptin may be involved, in the maintenance of estrous cyclicity. Our findings show that high levels of hypothalamic CRH disturb estrous cyclicity in the female animals and that the MC2R(-/-) female is a unique animal model of functional hypothalamic amenorrhea.

Anesthetic considerations for rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction (ROHHAD) syndrome in children.

PubMed

Chandrakantan, Arvind; Poulton, Thomas J

2013-01-01

Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction is an increasingly common diagnosis in patients who are being seen at tertiary care children's hospitals. We present two cases of anesthetics from the authors' own experience in addition to a comprehensive review of the disorder and anesthetic implications. © 2012 Blackwell Publishing Ltd.

Ovarian control of pituitary sensitivity of luteinizing hormone secretion to gonadotropin-releasing hormone in women with the polycystic ovary syndrome.

PubMed

Dafopoulos, Konstantinos; Venetis, Christos; Pournaras, Spyros; Kallitsaris, Athanasios; Messinis, Ioannis E

2009-10-01

This study investigated the ovarian control of LH responsiveness to GnRH in anovulatory women with the polycystic ovary syndrome (PCOS). It is suggested that the enhanced pituitary sensitivity of LH secretion to GnRH in anovulatory women with PCOS is not due to a reduced production but rather to a defect in the interaction of ovarian factors on the hypothalamic-pituitary system.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit.

PubMed

Larsen, P J; Seier, V; Fink-Jensen, A; Holst, J J; Warberg, J; Vrang, N

2003-03-01

Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocrine neurones. Adult male rats received a systemic injection of the neuronal tracer Fluorogold (FG) 2 days before fixation, and subsequent double- and triple-labelling immunoflourescence analysis demonstrated that neuroendocrine CART-containing neurones were present in the anteroventral periventricular, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro-opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland. Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42-89 immunoreactivity throughout the 90-min stimulation period. In contrast, the concentration of portal plasma CART immunoreactivity dropped in the vehicle infused rats. The current study provides further evidence that CART is a neuroendocrine-releasing factor with a possible impact on anterior pituitary function during states of haemodynamic stress.

A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

EPA Science Inventory

The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years.

PubMed

Secco, Andrea; di Iorgi, Natascia; Napoli, Flavia; Calandra, Erika; Ghezzi, Michele; Frassinetti, Costanza; Parodi, Stefano; Casini, Maria Rosaria; Lorini, Renata; Loche, Sandro; Maghnie, Mohamad

2009-11-01

Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.

Forever young: Endocrinology of paedomorphosis in the Mexican axolotl (Ambystoma mexicanum).

PubMed

De Groef, Bert; Grommen, Sylvia V H; Darras, Veerle M

2018-05-16

The Mexican axolotl (Ambystoma mexicanum) is a salamander species that does not undergo metamorphosis, resulting in the retention of juvenile characteristics in the mature breeding stage (paedomorphosis). Here we review the endocrinological studies investigating the proximate cause of axolotl paedomorphosis with a focus on the hypothalamo-pituitary-thyroid (HPT) axis. It is well established that axolotl paedomorphosis is a consequence of low activity of the HPT axis. The pituitary hormone thyrotropin (TSH) is capable of inducing metamorphosis in the axolotl, which indicates that all processes and interactions in the HPT axis below the pituitary level are functional, but that TSH release is impaired. In metamorphosing species, TSH secretion is largely controlled by the hypothalamic neuropeptide corticotropin-releasing hormone (CRH), which seems to have lost its thyrotropic activity in the axolotl. However, preliminary experiments have not yet confirmed a role for faulty CRH signalling in axolotl paedomorphosis. Other hypothalamic factors and potential pituitary inhibitors need to be investigated to identify their roles in amphibian metamorphosis and axolotl paedomorphosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

PubMed Central

Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

2015-01-01

Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

Proteomic Profiling of the Pituitary Gland in Studies of Psychiatric Disorders.

PubMed

Krishnamurthy, Divya; Rahmoune, Hassan; Guest, Paul C

2017-01-01

Psychiatric disorders have been associated with perturbations of the hypothalamic-pituitary-adrenal axis. Therefore, proteomic studies of the pituitary gland have the potential to provide new insights into the underlying pathways affected in these conditions as well as identify new biomarkers or targets for use in developing improved medications. This chapter describes a protocol for preparation of pituitary protein extracts followed by characterization of the pituitary proteome by label-free liquid chromatography-tandem mass spectrometry in expression mode (LC-MS E ). The main focus was on establishing a method for identifying the major pituitary hormones and accessory proteins as many of these have already been implicated in psychiatric diseases.

[Contributions of cortisol suppression tests to understanding of psychiatric disorders: a narrative review of literature].

PubMed

Tajima-Pozo, Kazuhiro; Montes-Montero, Ana; Güemes, Itziar; González-Vives, Sara; Díaz-Marsá, Marina; Carrasco, José Luis

2013-01-01

Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for detecting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis. Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Effects of neonatal hyperthyroidism on the development of the hypothalamic-pituitary-thyroid axis in the rat.

PubMed

Dussault, J H; Coulombe, P; Walker, P

1982-03-01

The acute and latent effects of neonatal hyperthyroidism (NH) on the hypothalamic-pituitary-thyroid axis were studied in the rat after treatment of newborn animals with L-T4 (0.4 microgram/g BW, daily) for a period of 12 days. NH was associated with a permanent reduction in body weight in both male and female rats, in addition to a delay in the attainment of peak concentrations of hypothalamic TRH and pituitary and serum TSH. Serum TSH, T4, and T3 concentrations also were significantly and permanently reduced in NH animals (P less than 0.01) after cessation of L-T4 treatment. The serum TSH secretory response to 1 microgram synthetic TRH also was evaluated in 120-day-old control and NH rats, before and after the administration of L-T4 (0.6 microgram/100 g BW for 7 days) or propylthiouracil (0.05% in the drinking water for 14 days). In the baseline state, adult NH rats had a net secretory response similar to that of controls (189.0 +/- 31.3 vs. 227.0 +/- 29.3 microgram/ml . min). Administration of T4 significantly decreased while propylthiouracil treatment significantly increased the net TSH secretory response of NH rats compared to similarly treated control rats. These data are compatible with the hypothesis that NH leads to a permanent resetting of the regulatory set-point for pituitary TSH secretion and to increased sensitivity to the feedback inhibitory effects of thyroid hormones.

[Granulomatosis with polyangiitis manifested as diabetes insipidus].

PubMed

Pátek, Ondřej; Horáčková, Miroslava; Vítová, Lenka; Horváth, Rudolf; Háček, Jaromír; Schück, Otto

The case report shows a surprising presentation of pulmonary granulomatosis with polyangiitis (GPA) through symptoms of diabetes insipidus (DI) with granulomatous infiltration of the pituitary gland. The pituitary hormonal dysfunction as a result of granulomatosis of the pituitary gland is rare. Several studies have demonstrated that the incidence of the pituitary dysfunction reaches approx. 1 % of the patients with GPA. However it is mostly presented in patients with the disease already diagnosed. The patient described by us had no clinical expressions of GPA in the respiratory tract. He presented with polyuria and polydipsia. It was not until a more detailed examination of these symptoms was performed that a focal lung disease was detected and diagnosed as GPA. diabetes insipidus - granulomatosis with polyangiitis - granulomatous infiltration of the pituitary gland - pituitary hormonal dysfunction.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Hypothalamic-Pituitary Axis Dysfunction in Survivors of Childhood CNS Tumors: Importance of Systematic Follow-Up and Early Endocrine Consultation.

PubMed

Chemaitilly, Wassim; Armstrong, Gregory T; Gajjar, Amar; Hudson, Melissa M

2016-12-20

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 11-year-old male with a history of metastatic tectal plate low-grade glioma who was diagnosed at age 2.8 years transferred his care to the long-term follow-up clinic. He completed treatment with multiagent chemotherapy-carboplatin, vincristine, temozolomide, procarbazine, lomustine, and thioguanine-at age 4.5 years and did not require radiotherapy. At primary diagnosis, he presented with hydrocephalus that required ventriculoperitoneal shunt placement, with a subsequent shunt revision at age 6 years. Residual metastatic tumors in the third and fourth ventricles and in the suprasellar region remained stable for more than 5 years. The patient achieved normal developmental milestones and was not taking medications. He was offered screening for hypothalamic-pituitary axis (HPA) dysfunction because of his suprasellar lesion. His height was at the 25th percentile for chronological age, with decline from the 50th percentile noted during the preceding 18 months ( Fig 1 , point c). Pubertal stage was Tanner 4 for pubic hair and penile size, which contrasted with small testes (4.5 mL). Pubic hair and voice changes were noticed 2 to 3 years before this visit. Plasma testosterone level was consistent with Tanner 4 (255 ng/dL = 8.9 nmol/L). An x-ray of the left hand revealed a notably advanced bone age of 15.5 years. Plasma free T4, thyroid-stimulating hormone (TSH), and 8 am cortisol levels were normal. The patient was referred to the endocrinology clinic where he was diagnosed with growth hormone deficiency and was started on replacement therapy. He reached his final adult height of 144.1 cm at age 13.3 years ( Fig 1 , point d).

Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.

PubMed

Shafia, Sakineh; Vafaei, Abbas Ali; Samaei, Seyed Afshin; Bandegi, Ahmad Reza; Rafiei, Alireza; Valadan, Reza; Hosseini-Khah, Zahra; Mohammadkhani, Raziyeh; Rashidy-Pour, Ali

2017-03-01

Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests, the effects of the combined treatment were similar to those of exercise alone, suggesting that exercise is the main factor in the beneficial effects of the combined therapy in PTSD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraperitoneal injection of neuropeptide Y (NPY) alters neurotrophin rat hypothalamic levels: Implications for NPY potential role in stress-related disorders.

PubMed

Gelfo, Francesca; De Bartolo, Paola; Tirassa, Paola; Croce, Nicoletta; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

2011-06-01

Neuropeptide Y (NPY) is a 36-amino acid peptide which exerts several regulatory actions within peripheral and central nervous systems. Among NPY actions preclinical and clinical data have suggested that the anxiolytic and antidepressant actions of NPY may be related to its antagonist action on the hypothalamic-pituitary-adrenal (HPA) axis. The neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins involved in the growth, survival and function of neurons. In addition to this, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has been proposed. To characterize the effect of NPY on the production of neurotrophins in the hypothalamus we exposed young adult rats to NPY intraperitoneal administration for three consecutive days and then evaluated BDNF and NGF synthesis in this brain region. We found that NPY treatment decreased BDNF and increased NGF production in the hypothalamus. Given the role of neurotrophins in the hypothalamus, these findings, although preliminary, provide evidence for a role of NPY as inhibitor of HPA axis and support the idea that NPY might be involved in pathologies characterized by HPA axis dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Cloning of the prepro C-RFa gene and brain localization of the active peptide in Salmo salar.

PubMed

Montefusco-Siegmund, R A; Romero, A; Kausel, G; Muller, M; Fujimoto, M; Figueroa, J

2006-08-01

In all vertebrates, the synthesis and release of prolactin (Prl) from pituitary lactotroph cells is tightly controlled by hypothalamic factors. We have cloned and characterized a hypothalamic cDNA from Atlantic salmon (Salmo salar) encoding C-RFa, a peptide structurally related to mammalian Prl-releasing peptide (PrRP). The deduced preprohormone precursor is composed of 155 amino acid residues presenting a 87.1% similarity to chum salmon C-RFa and a 100% similarity to all fish C-RFa in the bioactive precursor motifs. C-RFa-immunoreactive perikarya and fibres were located in the brain of S. salar, especially in the hypothalamus, olfactory tract, optic tectum and cerebellum. In contrast, immunolabelled fibres were not observed in the pituitary stalk or in the hypophysis. However, interestingly, we detected immunolabelled cells in the rostral pars distalis of the pituitary in the basolateral region in which Prl is synthesized. These results were confirmed by obtaining a strong signal by using reverse transcription/polymerase chain reaction (RT-PCR) on mRNA from both hypothalamus and pituitary. These data show, for the first time, by immunohistochemistry and RT-PCR, that C-RFa is produced in pituitary cells. Finally, based on these results, a possible function for C-RFa as a locally produced PrRP in this teleost is discussed.

The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.

PubMed

Astapova, Inna; Vella, Kristen R; Ramadoss, Preeti; Holtz, Kaila A; Rodwin, Benjamin A; Liao, Xiao-Hui; Weiss, Roy E; Rosenberg, Michael A; Rosenzweig, Anthony; Hollenberg, Anthony N

2011-02-01

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

PubMed

Krysiak, R; Szkrobka, W; Okopien, B

2015-04-01

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

PubMed

Graziani, Alessandro; Casalini, Pierpaolo; Mirici-Cappa, Federica; Pezzi, Giuseppe; Giuseppe Stefanini, Francesco

2016-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Pituitary gland and pregnancy.

PubMed

Foyouzi, Nastaran; Frisbaek, Yr; Norwitz, Errol R

2004-12-01

The hypothalamic-pituitary-adrenal axis is central to mammalian reproductive function, including conception, pregnancy maintenance, parturition, and breastfeeding. Pregnancy is associated with substantial physiologic changes within this endocrine axis to meet the demands of pregnancy, which include support of the fetus (volume support, nutritional and oxygen supply, clearance of fetal waste), protection of the fetus (from starvation, drugs, toxins), preparation of the uterus for labor, and protection of the mother from potential cardiovascular injury at delivery. This article reviews the anatomy, embryology, and physiology of the pituitary. The effect of pregnancy on pituitary structure and function, in health and disease, also is discussed.

Sleep characteristics as predictor variables of stress systems markers in insomnia disorder.

PubMed

Floam, Samantha; Simpson, Norah; Nemeth, Emese; Scott-Sutherland, Jennifer; Gautam, Shiva; Haack, Monika

2015-06-01

This study investigates the extent to which sleep characteristics serve as predictor variables for inflammatory, hypothalamic-pituitary-adrenal and autonomic systems markers. Twenty-nine participants with a diagnosis of insomnia disorder based on the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (age 25.3 ± 1.6 years, insomnia duration 6.6 ± 0.8 years) and 19 healthy control sleepers (age 25.4 ± 1.4 years) underwent a 2-week at-home evaluation keeping a sleep diary and wearing an actigraph, followed by a visit to the Research Center to measure blood pressure, and collect blood and urine samples. The actigraphy- and diary-based variables of sleep duration, sleep-onset latency, wake after sleep onset and sleep fragmentation/number of night-time awakenings were averaged and entered as dependent variables in regression analyses. Composite scores were calculated for the autonomic (blood pressure, norepinephrine), inflammatory (monocyte counts, interleukin-6, C-reactive protein) and hypothalamic-pituitary-adrenal systems (cortisol), and used as predictor variables in regression models. Compared with controls, individuals with insomnia had a shorter sleep duration (P < 0.05), and a higher hypothalamic-pituitary-adrenal and inflammatory composite score (P < 0.05). The higher inflammatory score was mainly due to higher circulating monocytes (P < 0.05), rather than differences in interleukin-6 or C-reactive protein. In persistent insomnia disorder, cortisol is upregulated and associated with actigraphy- and diary-based wake after sleep onset, suggesting that wake after sleep onset may serve as a marker to identify individuals at increased risks for disorders associated with a hyperactive hypothalamic-pituitary-adrenal system. The absence of autonomic and pro-inflammatory changes (interleukin-6, C-reactive protein), despite a substantial decrease in actigraphic sleep duration, may relate to a higher resilience to the adverse biological consequences of insomnia in this young age group. © 2014 European Sleep Research Society.

The prevalence of impaired glucose regulation in anxiety disorder patients and the relationship with hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-thyroid axis activity.

PubMed

Zhou, Yaling; Dong, Zaiquan; A, Ruhan; Liao, Zongbing; Guo, Jing; Liu, Cancan; Sun, Xueli

2016-08-29

To investigate the prevalence of impaired glucose regulation (IGR) in patients with anxiety disorders and the relationship with hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes function. From September 2013 to May 2015, a total of 646 patients with anxiety disorders who matched the criteria of the 10 th revision of the International Statistical Classification of Diseases and Related Health Problems participated in our study, which was conducted in the Psychiatric Inpatient Department of the West China Hospital of Sichuan University. The results from 75-g glucose tolerance tests, and morning (8:00 am) serum cortisol (PTC), adrenocorticotropic hormone༈ACTH), thyroid-stimulating hormone (TSH), TT3, TT4, FT3, and FT4 levels were collected. The Hamilton Anxiety Scale was administered to assess the severity of anxiety. SPSS 17.0 software was used for statistical analysis. The crude prevalence of impaired glucose regulation was 24.61% in patients with anxiety disorders patients. In the 18-40 year age group with impaired glucose regulation (IGR), both ACTH and PTC levels were higher than the control group (P<0.05). In the 61-75 year age group with IGR, the TSH level was lower and the FT4 level was higher than the control group (P<0.05). The results herein partially confirm that the prevalence of IGR in patients with anxiety disorders is high. Impaired glucose in the younger age group is closely associated with HPA axis function, while impaired glucose in the older age group is closely associated with HPT axis alteration. Therefore, routine blood glucose and endocrine function testing in patients with anxiety disorder is of clinical importance to prevent the development of diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hypothalamo-pituitary hormone insufficiency associated with cleft lip and palate.

PubMed Central

Roitman, A; Laron, Z

1978-01-01

Two male patients with congenital cleft lip and palate first seen at ages 10.2 and 21.5 years presented with typical signs of hypothalamic-interior pituitary hormone deficiencies. They were found to lack GH, LH, and FSH and to be partially deficient in TSH and ACTH. Several congenital defects may explain this rare syndrome affecting midline structures in the proximity of the maldeveloped palate, including Rathke's pouch, which migrates distally to develop into the anterior pituitary. PMID:747400

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

PubMed

De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

2000-05-01

To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

Sleep architecture and sleep apnea in patients with Cushing's disease.

PubMed

Shipley, J E; Schteingart, D E; Tandon, R; Starkman, M N

1992-12-01

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.

Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function.

PubMed

Haj-Mirzaian, A; Amiri, S; Kordjazy, N; Momeny, M; Razmi, A; Rahimi-Balaei, M; Amini-Khoei, H; Haj-Mirzaian, A; Marzban, H; Mehr, S E; Ghaffari, S H; Dehpour, A R

2016-02-19

The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Mothers' parenting stress is associated with salivary cortisol profiles in children with attention deficit hyperactivity disorder.

PubMed

Korpa, Terpsichori; Pervanidou, Panagiota; Angeli, Eleni; Apostolakou, Filia; Papanikolaou, Katerina; Papassotiriou, Ioannis; Chrousos, George P; Kolaitis, Gerasimos

2017-03-01

The aim of this study was to explore the relation between mothers' parenting stress and the functioning of the hypothalamic-pituitary-adrenal axis (HPAA), as expressed by daily salivary cortisol concentrations, in their children diagnosed with attention deficit hyperactivity disorder (ADHD). Seventy-five children aged 6-11 years diagnosed with ADHD predominant hyperactive-impulsive/combined (ADHD-HI/C, N = 49) and inattentive symptoms (ADHD-I, N = 26) and 45 healthy peers and their mothers participated in the study. Μothers completed measures assessing their children's ADHD status, perceived parenting stress (Parenting Stress Index - Short Form, PSI-SF), mothers' symptoms of psychopathology, social support and socioeconomic status. Children's salivary cortisol samples were collected at six different time points on a single day. Mothers of children with ADHD-HI/C reported higher levels of parenting stress than mothers of children with ADHD-I and controls. All PSI-SF subscales showed significant associations with children's cortisol awakening response (CAR) in both ADHD groups, with the exception of the parental distress subscale in the ADHD-I group. In both ADHD groups, the parent-child dysfunctional interaction subscale, the difficult child subscale and the PSI total score were significantly associated with children's CAR. An interrelation is revealed between mothers' high levels of parenting stress and HPAA functioning in children with ADHD. In this population, CAR has been identified as a sensitive peripheral measure of HPAA functioning in children. Lay summaryThis study showed that in families of children diagnosed with ADHD, there is a complex relation between the mothers' high levels of parenting stress and children's atypical hypothalamic-pituitary-adrenal axis functioning.

Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

PubMed Central

Lee, Jong-Ho; Kim, Jin Young

2014-01-01

Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis. PMID:25031890

A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

PubMed

Porcu, Eleonora; Medici, Marco; Pistis, Giorgio; Volpato, Claudia B; Wilson, Scott G; Cappola, Anne R; Bos, Steffan D; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M; Nolte, Ilja M; O'Connell, Jeffrey R; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J; Buckley, Brendan M; Camaschella, Clara; de Craen, Anton J M; Davies, Gail; de Visser, Marieke C H; Ford, Ian; Forsen, Tom; Frayling, Timothy M; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T; Hermus, Ad R; Hofman, Albert; Houwing-Duistermaat, Jeanine J; Jensen, Richard A; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D; Nagaraja, Ramaiah; Netea-Maier, Romana T; Palotie, Aarno; Persani, Luca; Piras, Maria G; Psaty, Bruce M; Räikkönen, Katri; Richards, J Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M; Sattar, Naveed; Shields, Beverley M; Soranzo, Nicole; Starr, John M; Stott, David J; Sweep, Fred C G J; Usala, Gianluca; van der Klauw, Melanie M; van Heemst, Diana; van Mullem, Alies; Vermeulen, Sita H; Visser, W Edward; Walsh, John P; Westendorp, Rudi G J; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J; Eriksson, Johan G; Ferrucci, Luigi; Fox, Caroline S; Jukema, J Wouter; Kiemeney, Lambertus A; Pramstaller, Peter P; Schlessinger, David; Shuldiner, Alan R; Slagboom, Eline P; Uitterlinden, André G; Vaidya, Bijay; Visser, Theo J; Wolffenbuttel, Bruce H R; Meulenbelt, Ingrid; Rotter, Jerome I; Spector, Tim D; Hicks, Andrew A; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Glucocorticoid Receptor Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder

PubMed Central

Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A.; Mann, J. John

2016-01-01

Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. PMID:27030168

GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

PubMed

Yin, Honglei; Galfalvy, Hanga; Pantazatos, Spiro P; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, J John

2016-06-01

We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. © 2016 Wiley Periodicals, Inc.

Dysmenorrhoea is associated with central changes in otherwise healthy women.

PubMed

Vincent, Katy; Warnaby, Catherine; Stagg, Charlotte J; Moore, Jane; Kennedy, Stephen; Tracey, Irene

2011-09-01

Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PubMed

Clement, S C; Schoot, R A; Slater, O; Chisholm, J C; Abela, C; Balm, A J M; van den Brekel, M W; Breunis, W B; Chang, Y C; Davila Fajardo, R; Dunaway, D; Gajdosova, E; Gaze, M N; Gupta, S; Hartley, B; Kremer, L C M; van Lennep, M; Levitt, G A; Mandeville, H C; Pieters, B R; Saeed, P; Smeele, L E; Strackee, S D; Ronckers, C M; Caron, H N; van Santen, H M; Merks, J H M

2016-02-01

Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.

PubMed

Armario, Antonio

2010-07-01

Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences. Copyright 2010 Elsevier Ltd. All rights reserved.

Pyrethroid Insecticide Cypermethrin Accelerates Pubertal Onset in Male Mice via Disrupting Hypothalamic-Pituitary-Gonadal Axis.

PubMed

Ye, Xiaoqing; Li, Feixue; Zhang, Jianyun; Ma, Huihui; Ji, Dapeng; Huang, Xin; Curry, Thomas E; Liu, Weiping; Liu, Jing

2017-09-05

Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models. Early postnatal exposure to CP at environmentally relevant doses (0.5, 5, and 50 μg/kg CP) significantly accelerated the age of puberty onset in male mice. Administration of CP induced a dose-dependent increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in male mice. CP did not affect gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus, but CP at higher concentrations stimulated GnRH pulse frequency. CP could induce the secretion of LH and FSH, as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ, and FSHβ] in pituitary gonadotropes. CP stimulated testosterone production and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in testicular Leydig cells. The interference with hypothalamic sodium channels as well as calcium channels in pituitary gonadotropes and testicular Leydig cells was responsible for CP-induced HPG axis maturation. Our findings established in animal models provide further evidence for the biological plausibility of pyrethroid exposure as a potentially environmental contributor to earlier puberty in males.

Development of the hypothalamus and pituitary in platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus)

PubMed Central

Ashwell, Ken W S

2012-01-01

The living monotremes (platypus and echidnas) are distinguished by the development of their young in a leathery-shelled egg, a low and variable body temperature and a primitive teat-less mammary gland. Their young are hatched in an immature state and must deal with the external environment, with all its challenges of hypothermia and stress, as well as sourcing nutrients from the maternal mammary gland. The Hill and Hubrecht embryological collections have been used to follow the structural development of the monotreme hypothalamus and its connections with the pituitary gland both in the period leading up to hatching and during the lactational phase of development, and to relate this structural maturation to behavioural development. In the incubation phase, development of the hypothalamus proceeds from closure of the anterior neuropore to formation of the lateral hypothalamic zone and putative medial forebrain bundle. Some medial zone hypothalamic nuclei are emerging at the time of hatching, but these are poorly differentiated and periventricular zone nuclei do not appear until the first week of post-hatching life. Differentiation of the pituitary is also incomplete at hatching, epithelial cords do not develop in the pars anterior until the first week, and the hypothalamo-neurohypophyseal tract does not appear until the second week of post-hatching life. In many respects, the structure of the hypothalamus and pituitary of the newly hatched monotreme is similar to that seen in newborn marsupials, suggesting that both groups rely solely on lateral hypothalamic zone nuclei for whatever homeostatic mechanisms they are capable of at birth/hatching. PMID:22512474

A cohort study found that white blood cell count and endocrine markers predicted preterm birth in symptomatic women.

PubMed

Campbell, M Karen; Challis, John R G; DaSilva, Orlando; Bocking, Alan D

2005-03-01

This cohort study investigated potential clinical and biochemical predictors of subsequent preterm birth in women presenting with threatened preterm labor. Subjects were 218 pregnant women admitted to hospital with a diagnosis of threatened preterm labor at 22-36 weeks gestation. Exclusion criteria were multiple pregnancy, fetal anomalies, diabetes mellitus, abruptio placenta, preeclampsia, intrauterine growth restriction, cervical dilatation > 4 cm, and clinical signs of infection. Analyses used logistic regression. The presence of ruptured membranes was the best predictor of birth within 48 hours. Other important predictors were maternal white blood cell count at 22-27 weeks gestation and maternal adrenocorticotropin and corticotropin-releasing hormone concentrations at 28-36 weeks gestation. Subclinical infection may be an important etiologic factor in preterm births of gestational age < 28 weeks. For those at > or = 28 weeks gestation, the findings support the etiologic role of activation of the fetal and/or maternal hypothalamic pituitary adrenal axis leading to preterm birth.

Dairy Food Consumption and Meal-Induced Cortisol Response Interacted to Influence Weight Loss in Overweight Women Undergoing a 12-Week, Meal-Controlled, Weight Loss Intervention1234

PubMed Central

Witbracht, Megan G.; Van Loan, Marta; Adams, Sean H.; Keim, Nancy L.; Laugero, Kevin D.

2013-01-01

Dairy food enhances weight loss in animal models, possibly by modifying the metabolic effects of cortisol. This study determined in overweight women (ages 20.0–45.9 y; n = 51) whether including dairy food in an energy-restricted diet affects cortisol concentrations and whether differences in provoked cortisol explain the magnitude of weight loss. Women received either an adequate amount of dairy food (AD), the equivalent of ≥711 mL/d milk, or a low amount of dairy food (LD), the equivalent to ≤238 mL/d milk, in a 12-wk, energy-restricted dietary intervention. Participants were tested in a 12-h laboratory visit, which included 2 standard meals and a dinner buffet that was consumed ad libitum. Salivary cortisol was measured from waking to bedtime. Energy restriction increased (P ≤ 0.04) the minimum and decreased (P ≤ 0.02) the diurnal amplitude in the salivary cortisol concentration from baseline to postintervention. Energy restriction enhanced the dinner meal–stimulated salivary cortisol response (DMR) (P ≤ 0.02) but only in the LD group. Compared with the LD treatment, the AD treatment induced (P ≤ 0.04) greater reductions in body weight and fat, but only in women characterized as having a baseline DMR (responders) (n = 26); weight and fat lost in the AD and LD groups were similar in nonresponders (n = 25). Overall, energy restriction dampened diurnal salivary cortisol fluctuations [symptomatic of hypothalamic-pituitary-adrenal (HPA) axis dysfunction] and enhanced dinner meal–stimulated salivary cortisol concentrations. The AD treatment prevented the latter. Furthermore, certain phenotypic markers of HPA axis function may help to expose the weight-reducing effects of consuming dairy food. PMID:23190756

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

PubMed

Wang, Limin; Wang, Qian; Li, Guimei; Liu, Wendong

2015-09-01

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

[Hypopituitarism following traumatic brain injury: diagnostic and therapeutic issues].

PubMed

Lecoq, A-L; Chanson, P

2015-10-01

Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Familial Pallister-Hall in adulthood.

PubMed

Talsania, Mitali; Sharma, Rohan; Sughrue, Michael E; Scofield, R Hal; Lim, Jonea

2017-10-01

Pallister Hall syndrome is autosomal dominant disorder usually diagnosed in infants and children. Current diagnostic criteria include presence of hypothalamic hamartoma, post axial polydactyly and positive family history, but the disease has variable manifestations. Herein we report Pallister Hall syndrome diagnosed in a family where both patients were adults. A 59 year old man developed seizures 4 years prior to our evaluation of him, at which time imaging showed a hypothalamic hamartoma. The seizures were controlled medically. He did well until he had visual changes after a traumatic head injury. Repeat MRI showed slight expansion of the mass with formal visual field testing demonstrating bitemporal hemianopsia. There was no evidence of pituitary dysfunction except for large urine volume. He underwent surgery to debulk the hamartoma and the visual field defects improved. There was no hypopituitarism post-operatively, and the polydyspia resolved. His 29 year old daughter also had seizures and hypothalamic hamartoma. Both patients had had polydactyly with prior surgical correction in childhood. The daughter underwent genetic testing, which revealed a previously undescribed heterozygous single base pair deletion in exon 13 of the GLI3 gene causing a frameshift mutation. Further investigation into family history revealed multiple members in previous generations with polydactyly and/or seizures. Pallister-Hall syndrome is caused by an inherited autosomal dominant or de novo mutation in GLI3 gene. This rare syndrome has not had prevalence defined, however. Generally, diagnoses are made in the pediatric population. Our report adds to the few cases detected in adulthood.

[Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

PubMed

Góth, Miklós; Hubina, Erika; Korbonits, Márta

2005-01-09

The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

Impaired Pituitary Axes Following Traumatic Brain Injury

PubMed Central

Scranton, Robert A.; Baskin, David S.

2015-01-01

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed. PMID:26239686

High Fat Diet Dysregulates Hypothalamic-Pituitary Axis Gene Expression Levels which are Differentially Rescued by EPA and DHA Ethyl Esters.

PubMed

Shaikh, Saame Raza; Shaver, Patti R; Shewchuk, Brian M

2018-05-08

Dietary fat composition can modulate gene expression in peripheral tissues in obesity. Observations of the dysregulation of growth hormone (GH) in obesity indicate that these effects extend to the hypothalamic-pituitary (H-P) axis. The authors thus determine whether specific high fat (HF) diets influence the levels of Gh and other key gene transcripts in the H-P axis. C57BL/6 mice are fed a lean control diet or a HF diet in the absence or presence of OA, EPA, or DHA ethyl esters. Comparative studies are conducted with menhaden fish oil. The HF diet lowered pituitary Gh mRNA and protein levels, and cell culture studies reveal that elevated insulin and glucose can reduce Gh transcripts. Supplementation of the HF diet with OA, EPA, DHA, or menhaden fish oil do not improve pituitary Gh levels. The HF diet also impaired the levels of additional genes in the pituitary and hypothalamus, which are selectively rescued with EPA or DHA ethyl esters. The effects of EPA and DHA are more robust relative to fish oil. A HF diet can affect H-P axis transcription, which can be mitigated in some genes by EPA and DHA, but not fish oil in most cases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.

PubMed

Birkebaek, Niels Holtum; Patel, Leena; Wright, Neville Bryce; Grigg, John Russell; Sinha, Smeeta; Hall, Catherine Margaret; Price, David Anthony; Lloyd, Ian Christopher; Clayton, Peter Ellis

2004-10-01

To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

PubMed

Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

2017-01-15

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

Brain-Heart Interaction: Cardiac Complications After Stroke.

PubMed

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Impact of the hypothalamic-pituitary-adrenal/gonadal axes on trajectory of age-related cognitive decline.

PubMed

Conrad, Cheryl D; Bimonte-Nelson, Heather A

2010-01-01

Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are declarative and spatial memories. The hippocampus facilitates the formation of declarative and spatial memories. Notably, the hippocampus is particularly vulnerable to aging. Genetic predisposition and lifetime experiences and exposures contribute to the aging process, brain changes and subsequent cognitive outcomes. In this review, two factors to which an individual is exposed, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, will be considered regarding the impact of age on hippocampal-dependent function. Spatial memory can be affected by cumulative exposure to chronic stress via glucocorticoids, released from the HPA axis, and from gonadal steroids (estrogens, progesterone and androgens) and gonadotrophins, released from the HPG axis. Additionally, this review will discuss how these hormones impact age-related hippocampal function. We hypothesize that lifetime experiences and exposure to these hormones contribute to the cognitive makeup of the aged individual, and contribute to the heterogeneous aged population that includes individuals with cognitive abilities as astute as their younger counterparts, as well as individuals with severe cognitive decline or neurodegenerative disease. Copyright 2010 Elsevier B.V. All rights reserved.

Effect of endotoxin on the expression of GnRH and GnRHR genes in the hypothalamus and anterior pituitary gland of anestrous ewes.

PubMed

Herman, Andrzej Przemysław; Tomaszewska-Zaremba, Dorota

2010-07-01

An immune/inflammatory challenge can affect reproduction at the level of the hypothalamus, pituitary gland, or gonads. Nonetheless, the major impact is thought to occur within the brain or the pituitary gland. The present study was designed to examine the effect of intravenous (i.v.) lipopolysaccharide (LPS) injection on the expression of gonadotropin-releasing hormone (GnRH) and the gonadotropin-releasing hormone receptor (GnRHR) genes in the hypothalamic structures where GnRH neurons are located as well as in the anterior pituitary gland (AP) of anestrous ewes. We also determined the effect of LPS on luteinizing hormone (LH) release. It was found that i.v. LPS injection significantly decreased GnRH and GnRHR mRNAs levels in the preoptic area (40%, p

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

PubMed Central

Xu, Jing; Huang, Wei; Zhong, Chengrong; Luo, Daji; Li, Shuangfei; Zhu, Zuoyan; Hu, Wei

2011-01-01

Background The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. Methodology/Principal Findings In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. Conclusions/Significance This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish. PMID:21695218

Serotonin involvement in pituitary-adrenal function

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

1977-01-01

Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats*

PubMed Central

Toorie, Anika M.; Cyr, Nicole E.; Steger, Jennifer S.; Beckman, Ross; Farah, George; Nillni, Eduardo A.

2016-01-01

Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH. PMID:26755731

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

PubMed

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase.

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

PubMed Central

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

Development of the hypothalamus and pituitary in platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).

PubMed

Ashwell, Ken W S

2012-07-01

The living monotremes (platypus and echidnas) are distinguished by the development of their young in a leathery-shelled egg, a low and variable body temperature and a primitive teat-less mammary gland. Their young are hatched in an immature state and must deal with the external environment, with all its challenges of hypothermia and stress, as well as sourcing nutrients from the maternal mammary gland. The Hill and Hubrecht embryological collections have been used to follow the structural development of the monotreme hypothalamus and its connections with the pituitary gland both in the period leading up to hatching and during the lactational phase of development, and to relate this structural maturation to behavioural development. In the incubation phase, development of the hypothalamus proceeds from closure of the anterior neuropore to formation of the lateral hypothalamic zone and putative medial forebrain bundle. Some medial zone hypothalamic nuclei are emerging at the time of hatching, but these are poorly differentiated and periventricular zone nuclei do not appear until the first week of post-hatching life. Differentiation of the pituitary is also incomplete at hatching, epithelial cords do not develop in the pars anterior until the first week, and the hypothalamo-neurohypophyseal tract does not appear until the second week of post-hatching life. In many respects, the structure of the hypothalamus and pituitary of the newly hatched monotreme is similar to that seen in newborn marsupials, suggesting that both groups rely solely on lateral hypothalamic zone nuclei for whatever homeostatic mechanisms they are capable of at birth/hatching. © 2012 The Author. Journal of Anatomy © 2012 Anatomical Society.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

Elite athletes and pubertal delay.

PubMed

Kapczuk, Karina

2017-10-01

Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes' pubertal development. On the other hand, pubertal timing, early or late, may impact on an athlete selection for a particular sport. Genetic predisposition, training load, nutritional status and psychological stress determine athletes' pubertal timing. Athletes that practice esthetic sports, especially gymnasts, are predisposed to a delay in pubertal development. The growing evidence indicates that energy deficiency, not a systemic training per se, plays a crucial role in the pathogenesis of functional hypothalamic hypogonadism in female athletes. Metabolic and psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and a targeted treatment. Somatic growth and sexual maturation of elite female athletes are largely sport-specific since each sport favors a particular somatotype and requires a specific training. Chronic negative energy balance resulting from a systemic physical training and inadequate energy intake may delay pubertal development in elite athletes. Youth athletes, especially those engaged in competitive sports that emphasize prepubertal or lean appearance, are at risk of developing relative energy deficiency in sport associated with disordered eating or eating disorders. Management strategies should address the complex conditions underlying functional hypothalamic hypogonadism.

Pituitary gene mutations and the growth hormone pathway.

PubMed

Moseley, C T; Phillips, J A

2000-01-01

Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

PubMed

Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

2016-03-01

Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Putative neuroprotective agents in neuropsychiatric disorders.

PubMed

Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael

2013-04-05

In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship between gut and sepsis: Role of ghrelin

PubMed Central

Das, Undurti N

2011-01-01

Ghrelin is a growth hormone secretagogue produced by the gut, and is expressed in the hypothalamus and other tissues as well. Ghrelin not only plays an important role in the regulation of appetite, energy balance and glucose homeostasis, but also shows anti-bacterial activity, suppresses pro-inflammatory cytokine production and restores gut barrier function. In experimental animals, ghrelin has shown significant beneficial actions in preventing mortality from sepsis. In the critically ill, corticosteroid insufficiency as a result of dysfunction of the hypothalamic-pituitary-adrenal axis is known to occur. It is therefore possible that both gut and hypothalamus play an important role in the pathogenesis of sepsis by virtue of their ability to produce ghrelin, which, in turn, could be a protective phenomenon to suppress inflammation. It remains to be seen whether ghrelin and its analogues are of benefit in treating patients with sepsis. PMID:21537444

Male hypogonadism.

PubMed

Basaria, Shehzad

2014-04-05

Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal amounts of sperm, or both. Hypogonadism may arise from testicular disease (primary hypogonadism) or dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical presentations vary dependent on the time of onset of androgen deficiency, whether the defect is in testosterone production or spermatogenesis, associated genetic factors, or history of androgen therapy. The clinical diagnosis of hypogonadism is made on the basis of signs and symptoms consistent with androgen deficiency and low morning testosterone concentrations in serum on multiple occasions. Several testosterone-replacement therapies are approved for treatment and should be selected according to the patient's preference, cost, availability, and formulation-specific properties. Contraindications to testosterone-replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment should be monitored for benefits and adverse effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

PubMed

Casanueva, F F; Micic, D; Pombo, M; Leal, A; Bokser, L; Zugaza, J L; Dieguez, C

1996-08-01

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

[Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities].

PubMed

Tatsumi, K; Amino, N; Miyai, K

1993-05-01

Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

The diagnosis of children with central diabetes insipidus.

PubMed

Ghirardello, Stefano; Garrè, Maria-Luisa; Rossi, Andrea; Maghnie, Mohamad

2007-03-01

Central diabetes insipidus is the end result of a number of different diseases that affect the hypothalamic-neurohypophyseal system. In many patients, especially children and young adults, it is caused by the destruction or degeneration of neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. The known causes of these lesions include germinoma or craniopharyngioma; Langerhans cell histiocytosis; local inflammatory, autoimmune or vascular diseases; trauma resulting from surgery or an accident; sarcoidosis; metastases; and midline cerebral and cranial malformations. In rare cases, genetic defects in AVP synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits are the underlying cause. Accurate diagnostic differentiation is essential for both safe and effective disease management. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress, as needed, to more sophisticated methods. Indeed, magnetic resonance imaging (MRI) represents the examination method of choice for evaluating hypothalamic-pituitary-related endocrine diseases due to its ability to provide strongly-contrasted high-resolution multi-planar and spatial images. Specifically, MRI allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered to be a clear marker of neurohypophyseal functional integrity, together with careful analysis of pituitary stalk shape and size, have provided the most striking recent findings contributing to the diagnosis and understanding of some forms of 'idiopathic' central diabetes insipidus.

How to recognize late-onset hypogonadism in men with sexual dysfunction

PubMed Central

Corona, Giovanni; Rastrelli, Giulia; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2012-01-01

Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels. PMID:22286862

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus.

PubMed

Morsi, Amr; DeFranco, Donald; Witchel, Selma

2018-06-06

Glucocorticoids (GCs), cortisol in humans, influence multiple essential maturational events during gestation. In the human fetus, fetal hypothalamic-pituitary-adrenal (HPA) axis function, fetal adrenal steroidogenesis, placental 11β- hydroxysteroid dehydrogenase type 2 activity, maternal cortisol concentrations, and environmental factors impact fetal cortisol exposure. The beneficial effects of synthetic glucocorticoids (sGCs), such as dexamethasone and betamethasone, on fetal lung maturation have significantly shifted the management of preterm labor and threatened preterm birth. Accumulating evidence suggests that exposure to sGCs in utero at critical developmental stages can alter the function of organ systems and that these effects may have sequelae that extend into adult life. Maternal stress and environmental influences may also impact fetal GC exposure. This article explores the vulnerability of the fetal HPA axis to endogenous GCs and exogenous sGCs. © 2018 S. Karger AG, Basel.

Social Stress and the Reactivation of Latent Herpes Simplex Virus Type 1

NASA Astrophysics Data System (ADS)

Padgett, David A.; Sheridan, John F.; Dorne, Julianne; Berntson, Gary G.; Candelora, Jessica; Glaser, Ronald

1998-06-01

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpes-viruses.

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Evaluation of Newly Developed Chemical Castration Method: Changes in Hormone Gene Expression of Hypothalamic-Pituitary Axis

PubMed Central

Kwak, Byung Kuk; Lee, Sung-Ho

2017-01-01

ABSTRACT Surgical castration (also known as orchidectomy, ORX) has been frequently performed to avoid uncontrolled breeding. However, it has some serious disadvantages. Several laboratories have developed chemical castration methods, using bilateral intratesticular injection (BITI) of simple chemical solutions. The present study was undertaken to compare the effects of ORX and of hypertonic saline BITI on the androgen-sensitive tissues such as pituitary and hypothalamus. Serum testosterone (T) levels of ORX animals and hypertonic saline BITI animals (SAL) after 4 weeks of the manipulations exhibited significantly drops as compared with the levels of intact animals (Intact:ORX:SAL = 7.74± 1.31:1.34±0.19:1.28±0.18 ng/ml, p<0.001). Both ORX and BITI method induced similar stimulatory effects on the pituitary gonadotropin subunits and hypothalamic KiSS-1 gene expressions. In contrast, the effects of ORX and hypertonic saline BITI on hypothalamic GnRH gene expression were different from these gene expressions, shown an inverse relationship between the two groups (Intact:ORX:SAL = 1:0.45±0.06:1:2.07±0.41:1.51±0.37 AU; ORX, p<0.001; SAL, p<0.05). In conclusion, we provided evidence that hypertonic saline BITI method has equivalent efficacy of T depletion to surgical castration in rats. The present study suggests the hypertonic saline BITI could be a promising substitute to conventional surgical castration. PMID:29082346

Quantitative analysis of in-vivo responses of reproductive and thyroid endpoints in male goldfish exposed to monocrotophos pesticide.

PubMed

Zhang, Xiaona; Liu, Wei; Wang, Jun; Tian, Hua; Wang, Wei; Ru, Shaoguo

2018-09-01

Cross-regulation occurs at many points between the hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes. Monocrotophos (MCP) pesticide could disrupt HPG and HPT axes, but its direct target within the endocrine system is still unclear. In the present study, hormone concentrations and transcriptional profiles of HPG and HPT genes were examined in male goldfish (Carassius auratus) exposed to 0, 4, 40, and 400 μg/L MCP for 2, 4, 8, and 12 d. In vivo data were analyzed by multiple linear regression and correlation analysis, quantitatively indicating that MCP-induced plasma 17β-estradiol (E 2 ) levels were most associated with alteration of cyp19a transcription, which was also a potential point indirectly modulated by the MCP-altered thyroid hormones (THs) status; disturbance of THs pathways was most related with effect of MCP on regulation of the hypothalamic-pituitary hormones involved in the thyroid system, and the increased E 2 levels might enhance the impact of MCP on HPT axis by modulating hepatic deiodinase expression. Our finding, based on these correlational data, gave a whole view of the regulations, especially on the cross-talk between sex hormone and thyroid hormone pathways upon exposure to chemicals with unknown direct target in vivo, and cautions should be exercised when developing adverse outcome pathway networks for reproductive and thyroidal endocrine disruption. Copyright © 2018 Elsevier Inc. All rights reserved.

BIOMARKERS for CHRONIC FATIGUE

PubMed Central

Broderick, Gordon; Fletcher, Mary Ann

2012-01-01

Fatigue that persists for 6 months or more is termed chronic fatigue. Chronic fatigue (CF) in combination with a minimum of 4 of 8 symptoms and the absence of diseases that could explain these symptoms, constitute the case definition for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Inflammation, immune system activation, autonomic dysfunction, impaired functioning in the hypothalamic-pituitary-adrenal axis, and neuroendocrine dysregulation have all been suggested as root causes of fatigue. The identification of objective markers consistently associated with CFS/ME is an important goal in relation to diagnosis and treatment, as the current case definitions are based entirely on physical signs and symptoms. This review is focused on the recent literature related to biomarkers for fatigue associated with CFS/ME and, for comparison, those associated with other diseases. These markers are distributed across several of the body’s core regulatory systems. A complex construct of symptoms emerges from alterations and/or dysfunctions in the nervous, endocrine and immune systems. We propose that new insight will depend on our ability to develop and deploy an integrative profiling of CFS/ME pathogenesis at the molecular level. Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited. PMID:22732129

[Impact of end-stage renal disease and kidney transplantation on the reproductive system].

PubMed

Delesalle, A-S; Robin, G; Provôt, F; Dewailly, D; Leroy-Billiard, M; Peigné, M

2015-01-01

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Perioperative management of the hypothalamic-pituitary-adrenal axis in patients with pituitary adenomas: an Australasian survey.

PubMed

Joseph, S P; Ho, J T; Doogue, M P; Burt, M G

2012-10-01

There is limited consensus regarding optimal glucocorticoid administration for pituitary surgery to prevent a potential adrenal crisis. To assess the investigation and management of the hypothalamic-pituitary-adrenal (HPA) axis in patients undergoing trans-sphenoidal hypophysectomy in Australasia. A questionnaire was sent to one endocrinologist at each of 18 centres performing pituitary surgery in Australasia. Using hypothetical case vignettes, respondents were asked to describe their investigation and management of the HPA axis for a patient with a: non-functioning macroadenoma and intact HPA axis, non-functioning macroadenoma and HPA deficiency and growth hormone secreting microadenoma undergoing trans-sphenoidal hypophysectomy. Responses were received from all 18 centres. Seventeen centres assess the HPA axis preoperatively by measuring early morning cortisol or a short synacthen test. Preoperative evaluation of the HPA status influenced glucocorticoid prescription by 10 centres, including 2/18 who would not prescribe perioperative glucocorticoids for a patient with a macroadenoma and an intact HPA axis. Tumour size influenced glucocorticoid prescribing patterns at 7/18 centres who prescribe a lower dose or no glucocorticoids for a patient with a microadenoma. Choice of investigations for definitive postoperative assessment of the HPA axis varied with eight centres requesting an insulin tolerance test, four centres a 250 µg short synacthen test and six centres requesting other tests. There is wide variability in the investigation and management of perioperative glucocorticoid requirements for patients undergoing pituitary surgery in Australasia. This may reflect limited evidence to define optimal management and that further well-designed studies are needed. © 2011 The Authors; Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Risk-adapted treatment and follow-up management in childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L

2016-05-01

Craniopharyngiomas are rare embryonic malformations of the sellar/parasellar region with low histological grade. Here, we review findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients. Clinical manifestations develop from increased intracranial pressure, anterior visual pathway damage, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized (no anatomical involvement with the hypothalamic and optical structures) therapy of choice is complete resection, meticulously performed to preserve hypothalamic and optic functions. In patients with unfavorable tumor involvement, optimal therapy is limited hypothalamus-sparing surgical strategy, followed by judicious irradiation dosage to minimize recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas result in serious sequelae, mainly hypothalamic syndrome. Craniopharyngioma is a chronic disease and must be managed as such, providing ongoing care of pediatric and adult patients by experienced multidisciplinary teams in the context of multicenter trials.

Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.

PubMed

Kempers, Marlies J E; van Tijn, David A; van Trotsenburg, A S Paul; de Vijlder, Jan J M; Wiedijk, Brenda M; Vulsma, Thomas

2003-12-01

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T(4) supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves' disease is preserving euthyroidism throughout pregnancy.

Interpretation of serum gonadotropin levels in hyperprolactinemia.

PubMed

Abbara, Ali; Clarke, Sophie A; Nesbitt, Alexander; Ali, Sabreen; Comninos, Alexander N; Hatfield, Emma; Martin, Niamh; Sam, Amir; Meeran, Karim; Dhillo, Waljit S

2018-04-16

Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.
. ©2018S. Karger AG, Basel.

Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone.

PubMed

Granata, Riccarda; Isgaard, Jörgen; Alloatti, Giuseppe; Ghigo, Ezio

2011-05-01

In 1976, small peptide growth hormone secretagogues (GHSs) were discovered and found to promote growth hormone (GH) release from the pituitary. The GHS receptor (GHS-R) was subsequently cloned, and its endogenous ligand ghrelin was later isolated from the stomach. Ghrelin is a 28-amino acid peptide, whose acylation is essential for binding to GHS-R type 1a and for the endocrine functions, including stimulation of GH secretion and subsequent food intake. Unacylated ghrelin, the other ghrelin form, although devoid of GHS-R binding is an active peptide, sharing many peripheral effects with acylated ghrelin (AG). The ghrelin system is broadly expressed in myocardial tissues, where it exerts different functions. Indeed, ghrelin inhibits cardiomyocyte and endothelial cell apoptosis, and improves left ventricular (LV) function during ischemia-reperfusion (I/R) injury. In rats with heart failure (HF), ghrelin improves LV dysfunction and attenuates the development of cardiac cachexia. Similarly, ghrelin exerts vasodilatory effects in humans, improves cardiac function and decreases systemic vascular resistance in patients with chronic HF. Obestatin is a recently identified ghrelin gene peptide. The physiological role of obestatin and its binding to the putative GPR39 receptor are still unclear, although protective effects have been demonstrated in the pancreas and heart. Similarly to AG, the hypothalamic peptide growth hormone-releasing hormone (GHRH) stimulates GH release from the pituitary, through binding to the GHRH-receptor. Besides its proliferative effects in different cell types, at the cardiovascular level GHRH inhibits cardiomyocyte apoptosis, and reduces infarct size in both isolated rat heart after I/R and in vivo after myocardial infarction. Therefore, both ghrelin and GHRH exert cardioprotective effects, which make them candidate targets for therapeutic intervention in cardiovascular dysfunctions.

Lowered testosterone in male obesity: mechanisms, morbidity and management

PubMed Central

Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

2014-01-01

With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials. PMID:24407187

Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.

PubMed

Pombo, M; Barreiro, J; Peñalva, A; Peino, R; Dieguez, C; Casanueva, F F

1995-11-01

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Chapter 22: Female Reproductive Toxicology

EPA Science Inventory

The female reproductive system provides multiple targets for environmental toxicants with the hypothalamic-pituitary-ovarian axis. Moreover, the functional impact of a chemical can differ, depending on the species involved and the parameters of exposure. While cross-species compa...

Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

PubMed Central

Xiong, Fuxia; Zhang, Lubo

2012-01-01

Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

Effects of Barium Chloride Exposure on Hormones and Genes of the Hypothalamic-Pituitary-Gonad Axis, and Reproduction of Zebrafish (Danio rerio).

PubMed

Kwon, Bareum; Ha, Nayoung; Jung, Joeun; Kim, Pan-Gyi; Kho, Younglim; Choi, Kyungho; Ji, Kyunghee

2016-03-01

Adult zebrafish pairs were exposed to sub-lethal concentrations of BaCl2 for 21 days, and the effects on reproduction, sex steroid hormones, and transcription of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. The adverse effects on performances of F1 generation were further examined with or without subsequent exposure to BaCl2. Egg production was significantly decreased, and parental exposure to BaCl2 resulted in lesser rates of hatching. In males, exposure to BaCl2 resulted in greater concentrations of E2 along with greater mRNA expression of cyp19a. The results demonstrated that BaCl2 could modulate gene transcriptions and hormone production of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

Hypothyroidism after Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

PubMed

Inskip, Peter D; Veiga, Lene H S; Brenner, Alina V; Sigurdson, Alice J; Ostroumova, Evgenia; Chow, Eric J; Stovall, Marilyn; Smith, Susan A; Weathers, Rita E; Leisenring, Wendy; Robison, Leslie L; Armstrong, Gregory T; Sklar, Charles A; Lubin, Jay H

2018-05-15

While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 five-year survivors of childhood cancer diagnosed at 26 hospitals in the U.S. and Canada between 1970 and 1986 and followed through 2009, the occurrence of hypothyroidism was ascertained among 12,015 survivors through serial questionnaires. Radiation doses to the thyroid gland and pituitary gland were estimated from radiotherapy records. Binary outcome regression was used to estimate prevalence odds ratios for hypothyroidism at five years from diagnosis of childhood cancer and Poisson regression to model incidence rate ratios (RR) after the first five years. A total of 1,193 cases of hypothyroidism were observed, 777 (65%) of which occurred five or more years after cancer diagnosis. The cumulative proportion affected with hypothyroidism (prevalence at five years after cancer diagnosis plus incidence through 30 years after cancer diagnosis) was highest among five-year survivors of Hodgkin lymphoma (32.3%; 95% CI: 29.5-34.9) and cancers of the central nervous system (17.7%; 95% CI: 15.2-20.4). The incidence rate was significantly associated with radiation dose to the thyroid and pituitary. The joint association of hypothyroidism with thyroid and pituitary dose was sub-additive for pituitary doses greater than 16 Gy. In particular, a very strong thyroid radiation dose dependence at low-to-moderate pituitary/hypothalamic doses was diminished at high pituitary doses. Radiation-related risks were higher in males than females and inversely associated with age at exposure and time since exposure but remained elevated more than 25 years after exposure. Our findings indicated that hypothyroidism was significantly associated with treatment with bleomycin (RR = 3.4; 95% CI: 1.6-7.3) and the alkylating agents cyclohexyl-chloroethyl-nitrosourea (CCNU) (RR = 3.0; 95% CI: 1.5-5.3) and cyclophosphamide (RR = 1.3; 95% CI: 1.0-1.8), with a significant dose response for CCNU ( P < 0.01). The risk of hypothyroidism among childhood cancer survivors treated with radiation depends both on direct, dose-dependent radiation-induced damage to the thyroid gland and on dose-dependent indirect effects secondary to irradiation of the hypothalamic-pituitary axis. The dose-response relationship for each site depends on dose to the other. Radiation-related risk persists for more than 25 years after treatment. Treatment with certain chemotherapy agents may increase the risk of hypothyroidism.

An investigation of hypothalamic-pituitary-adrenal axis hyperactivity in anorexia nervosa: the role of CRH and AVP.

PubMed

Connan, Frances; Lightman, Stafford L; Landau, Sabine; Wheeler, Michael; Treasure, Janet; Campbell, Iain C

2007-01-01

We hypothesised that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in anorexia nervosa (AN) is associated with (a) elevated arginine vasopressin (AVP) activity and (b) enhanced pituitary sensitivity to AVP, as it is in depressive illness. 16 Healthy women and 18 women with active AN participated in a combined dexamethasone (DXM)/corticotrophin releasing hormone (CRH) challenge test and an AVP challenge test. This combination of tests is designed to assess the functional contribution of AVP to HPA axis activity. 10 of the active AN group repeated participation after weight gain. The cortisol response to AVP was reduced by 138% in the active AN group, suggesting an impairment of pituitary sensitivity to AVP, which began to normalise with weight gain. The cortisol and adreno-corticotrophin (ACTH) responses to the DXM/CRH test were not significantly enhanced in the active AN group, suggesting that there was no elevated endogenous AVP activity augmenting the response to CRH in AN. Weight gain was associated with blunting of the endocrine response to the DXM/CRH test, which may have been related to rising oestrogen levels. Thus, contrary to the hypotheses, we did not find (a) evidence of upregulated AVP activity or (b) enhanced pituitary sensitivity to AVP in AN. These findings suggest that the mechanism of HPA axis hyperactivity differs in depression and AN, with greater involvement of AVP in depressive disorder and perhaps more reliance on CRH to drive the axis in AN. The powerful anorexigenic effect of CRH could contribute to the severity of weight loss associated with AN.

Cushing's syndrome: from physiological principles to diagnosis and clinical care.

PubMed

Raff, Hershel; Carroll, Ty

2015-02-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic-pituitary-adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism--Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: a longitudinal cohort study in the general population.

PubMed

Tak, Lineke M; Bakker, Stephan J L; Rosmalen, Judith G M

2009-07-01

In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute to FSS is the function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study investigates the association of HPA-axis function with cross-sectional presence and prospective development of FSS in the general population. This study was performed in a population-based cohort of 741 male and female adults (mean age 53.1, S.D. 10.9). Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI) in which the presence of 43 FSS is surveyed. In addition to the total number of FSS, bodily system FSS clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general symptoms were constructed. HPA-axis function was assessed by measuring 24-h urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed approximately 2 years later. All analyses were adjusted for age, gender, body mass index, smoking, alcohol use, depression, exercise frequency, and urinary volume. Regression analysis detected no cross-sectional association between 24-h UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In addition, 24-h UFC excretion was not associated with any of the bodily system FSS clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population. We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population.

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

PubMed Central

Volpato, Claudia B.; Wilson, Scott G.; Cappola, Anne R.; Bos, Steffan D.; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M.; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M.; Nolte, Ilja M.; O'Connell, Jeffrey R.; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J.; Buckley, Brendan M.; Camaschella, Clara; de Craen, Anton J. M.; Davies, Gail; de Visser, Marieke C. H.; Ford, Ian; Forsen, Tom; Frayling, Timothy M.; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T.; Hermus, Ad R.; Hofman, Albert; Houwing-Duistermaat, Jeanine J.; Jensen, Richard A.; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M.; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D.; Nagaraja, Ramaiah; Netea-Maier, Romana T.; Palotie, Aarno; Persani, Luca; Piras, Maria G.; Psaty, Bruce M.; Räikkönen, Katri; Richards, J. Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M.; Sattar, Naveed; Shields, Beverley M.; Soranzo, Nicole; Starr, John M.; Stott, David J.; Sweep, Fred C. G. J.; Usala, Gianluca; van der Klauw, Melanie M.; van Heemst, Diana; van Mullem, Alies; H.Vermeulen, Sita; Visser, W. Edward; Walsh, John P.; Westendorp, Rudi G. J.; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J.; Eriksson, Johan G.; Ferrucci, Luigi; Fox, Caroline S.; Jukema, J. Wouter; Kiemeney, Lambertus A.; Pramstaller, Peter P.; Schlessinger, David; Shuldiner, Alan R.; Slagboom, Eline P.; Uitterlinden, André G.; Vaidya, Bijay; Visser, Theo J.; Wolffenbuttel, Bruce H. R.; Meulenbelt, Ingrid; Rotter, Jerome I.; Spector, Tim D.; Hicks, Andrew A.; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P.; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. PMID:23408906

Polycystic Ovary Syndrome: An Under-recognized Cause of Abnormal Uterine Bleeding in Adolescents Admitted to a Children's Hospital.

PubMed

Maslyanskaya, Sofya; Talib, Hina J; Northridge, Jennifer L; Jacobs, Amanda M; Coble, Chanelle; Coupey, Susan M

2017-06-01

To evaluate whether ovulatory dysfunction due to polycystic ovary syndrome (PCOS) is a common underlying etiology of abnormal uterine bleeding (AUB) in adolescents who require hospitalization and to explore etiology, treatment, and complications of AUB with severe anemia in adolescents. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We identified female patients aged 8-20 years admitted to a children's hospital for treatment of AUB from January 2000 to December 2014. Our hospital protocol advises hormonal testing for PCOS and other disorders before treatment for AUB. We reviewed medical records and recorded laboratory evaluations, treatments, and final underlying diagnoses as well as recurrences of AUB and readmissions in the subsequent year. Of the 125 subjects, the mean age was 16.5 ± 2.9 years; mean hemoglobin level was 7.0 ± 1.8 g/dL; 54% were overweight/obese; and 41% sexually active. PCOS accounted for 33% of admissions; hypothalamic pituitary ovarian axis immaturity 31%; endometritis 13%; bleeding disorders 10%. Girls with PCOS were more likely to be overweight/obese (74% vs 46%; P < .01) and girls with hypothalamic pituitary ovarian axis immaturity had lower hemoglobin levels (6.4 g/dL vs 7.4 g/dL; P < .05), than girls with all other etiologies of AUB. Treating physicians failed to diagnose endometritis as the etiology for AUB in 4 of 8 girls with positive tests for sexually transmitted infection and no other etiology. PCOS was the most common underlying etiology in adolescents hospitalized with AUB. Screening for hyperandrogenemia is important for early diagnosis of PCOS to allow ongoing management and prevention of comorbidities. Endometritis was frequently underestimated as an etiology for AUB. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp; Department of Radiology, Kanagawa Children's Medical Center, Yokohama; Omura, Motoko

2012-11-01

Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The medianmore » radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with GCT.« less

Efficacy and safety of bariatric surgery for craniopharyngioma-related hypothalamic obesity: a matched case-control study with 2 years of follow-up.

PubMed

Wijnen, M; Olsson, D S; van den Heuvel-Eibrink, M M; Wallenius, V; Janssen, J A M J L; Delhanty, P J D; van der Lely, A J; Johannsson, G; Neggers, S J C M M

2017-02-01

Hypothalamic obesity is a devastating consequence of craniopharyngioma. Bariatric surgery could be a promising therapeutic option. However, its efficacy and safety in patients with craniopharyngioma-related hypothalamic obesity remain largely unknown. We investigated the efficacy of bariatric surgery for inducing weight loss in patients with craniopharyngioma-related hypothalamic obesity. In addition, we studied the safety of bariatric surgery regarding its effects on hormone replacement therapy for pituitary insufficiency. In this retrospective matched case-control study, we compared weight loss after bariatric surgery (that is, Roux-en-Y gastric bypass and sleeve gastrectomy) between eight patients with craniopharyngioma-related hypothalamic obesity and 75 controls with 'common' obesity during 2 years of follow-up. We validated our results at 1 year of follow-up in a meta-analysis. In addition, we studied alterations in hormone replacement therapy after bariatric surgery in patients with craniopharyngioma. Mean weight loss after bariatric surgery was 19% vs 25% (difference -6%, 95% confidence of interval (CI) -14.1 to 4.6; P=0.091) at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity compared with control subjects with 'common' obesity. Mean weight loss was 25% vs 29% (difference -4%, 95% CI -11.6 to 8.1; P=0.419) after Roux-en-Y gastric bypass and 10% vs 20% (difference -10%, 95% CI -14.1 to -6.2; P=0.003) after sleeve gastrectomy at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity vs control subjects with 'common' obesity. Our meta-analysis demonstrated significant weight loss 1 year after Roux-en-Y gastric bypass, but not after sleeve gastrectomy. Seven patients with craniopharyngioma suffered from pituitary insufficiency; three of them required minor adjustments in hormone replacement therapy after bariatric surgery. Weight loss after Roux-en-Y gastric bypass, but not sleeve gastrectomy, was comparable between patients with craniopharyngioma-related hypothalamic obesity and control subjects with 'common' obesity at 2 years of follow-up. Bariatric surgery seems safe regarding its effects on hormone replacement therapy.

Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

PubMed

Jedraszak, Guillaume; Braun, Karine; Receveur, Aline; Decamp, Matthieu; Andrieux, Joris; Rabbind Singh, Amrathlal; Copin, Henri; Bremond-Gignac, Dominique; Mathieu, Michèle; Rochette, Jacques; Morin, Gilles

2015-10-01

Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Residual symptoms in depression an emerging therapeutic concept.

PubMed

Sonino, Nicoletta; Fava, Giovanni A

2002-05-01

Cushing's syndrome is due to chronic glucocorticoid excess that may have various etiologies. The most common endogenous form is pituitary-dependent bilateral adrenal hyperplasia, which is termed Cushing's disease. Major depression occurs in more than half of the cases. The presence of depressive symptoms connotes severity of clinical presentation and, in patients with hypothalamic-pituitary forms, entails prognostic value. Medical treatment may be used while awaiting more definitive solutions for the illness by surgery. The inhibitors of steroid production (e.g., ketoconazole, metyrapone and aminoglutethimide), rather than antidepressant drugs, are generally successful in lifting depression as well as other disabling symptoms. Since central serotonergic regulation could have a role in the course of Cushing's disease, serotonin antagonists (e.g., cyproheptadine, ritanserin and ketanserin) have been employed. Findings related to the pharmacological response of depression in Cushing's disease were found to have implications for the pathophysiology of depression and the potential involvement of the hypothalamic-pituitary-adrenal axis (HPA axis) in resistance and tolerance to antidepressant drugs. The use of serotonergic drugs in Cushing's disease may yield important insights in the understanding of serotonergic regulation both in Cushing's disease and in the HPA axis in nonendocrine major depression.

Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus.

PubMed

Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

2015-03-01

This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis.

Hedgehog signaling: endocrine gland development and function.

PubMed

Cohen, M Michael

2010-01-01

The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

Developmental abnormalities of the posterior pituitary gland.

PubMed

di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

2009-01-01

While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

Newly developed central diabetes insipidus following kidney transplantation: a case report.

PubMed

Kim, K M; Kim, S M; Lee, J; Lee, S Y; Kwon, S K; Kim, H-Y

2013-09-01

Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency.

PubMed

di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna; Secco, Andrea; Calandra, Erika; Calcagno, AnnaLisa; Frassinetti, Costanza; Ghezzi, Michele; Ambrosini, Linda; Parodi, Stefano; Gastaldi, Roberto; Loche, Sandro; Maghnie, Mohamad

2010-05-01

The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.

Attenuated Stress Response to Acute Restraint and Forced Swimming Stress in Arginine Vasopressin 1b Receptor Subtype (Avpr1b) Receptor Knockout Mice and Wild-Type Mice Treated with a Novel Avpr1b Receptor Antagonist

PubMed Central

Roper, J A; Craighead, M; O’Carroll, A-M; Lolait, S J

2010-01-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. PMID:20846299

Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

PubMed

Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

2010-11-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

PubMed

Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

2015-06-01

Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

PubMed

Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

2015-11-01

The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.

Attachment Strategies and Neuroendocrine Biomarkers in Obese Children.

PubMed

Pinto, Inês; Wilkinson, Simon; Virella, Daniel; Alves, Marta; Calhau, Conceição; Coelho, Rui

2016-05-01

Quality of the parent-infant relationship influences the mechanisms of development of the child's physiological stress regulation. This study explored associations between attachment strategies and both cortisol and thyroid stimulating hormone, hypothesized to be respectively a potential mediator and a potential intervening variable of the mother-child relationship in obese children. A sample of 83 obese children (46 boys), aged 10.9 (1.8) years was recruited from a child obesity clinic. Obesity was defined by body mass index percentile adjusted for age and sex. Metabolic biomarkers were measured by routine methods. Attachment strategies were assessed with self and parent-report questionnaires. Family functioning was assessed with parent-reported questionnaires (FACES-III). Multivariate linear regression analyses were performed. Type A, avoidant attachment strategies, had significant positive association with thyroid stimulating hormone levels and negative association with cortisol levels (R2 = 0.352). Type B, secure attachment strategies, had significant positive associations with both hypothyroidism and body mass index percentile (R2 = 0.541). 'Insecure attachment' (types A and C combined) strategies showed some evidence of positive association with thyroid stimulating hormone (R2 = 0.250). These findings suggest that there may be commonalities in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes. Processes involved in development of the type A attachment strategy appear to be associated with effects on the regulatory mechanisms of the hypothalamic-pituitary-adrenal axis. In obese children, different attachment strategies are associated with diverse metabolic profiles. How this may contribute to developing differentiated treatment approaches remains to be explored.

Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary-adrenal axis.

PubMed

Colagiovanni, Dorothy B; Drolet, Daniel W; Dihel, Larry; Meyer, Dennis J; Hart, Karen; Wolf, Julie

2006-01-01

4'-Thio-beta-D-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression, reversible transaminase elevations, and flu-like symptoms are common side effects associated with human use of gemcitabine and ara-C. Fatigue is also associated with the use of gemcitabine and OSI-7836 in humans. To better understand the toxicity of OSI-7836, subchronic studies were conducted in dogs. OSI-7836 was administered on days 1 and 8 or on days 1, 2, and 3 of a 21-day dose regimen. These schedules attempted to match clinical trial dosing regimens. Routine toxicity study end points demonstrated that OSI-7836 was primarily cytotoxic to the gastrointestinal tract, bone marrow, and testes; the myelotoxicity was mild and reversible. Plasma pharmacokinetics were dose-linear with an elimination half-life of 2.2 h. Follow-up single dose experiments in dogs assessed drug effects on lymphocyte subpopulations and on adrenal and thyroid function. Populations of T and B cells were equally reduced following OSI-7836 administration. There were no adverse effects on thyroid function, but there were marked reductions in circulating cortisol and adrenocorticotropic hormone concentrations suggesting a centrally mediated impairment of the hypothalamic-pituitary-adrenal axis. These findings show a toxicological profile with OSI-7836 similar to other nucleoside analogues and suggest that the beagle is a model for studying one possible cause of OSI-7836-related fatigue, impaired function of the hypothalamic-pituitary-adrenal axis.

Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis

PubMed Central

Morillo-Bernal, Jesús; Fernández-Santos, José M; Utrilla, José C; de Miguel, Manuel; García-Marín, Rocío; Martín-Lacave, Inés

2009-01-01

Thyroid C cells, or parafollicular cells, are mainly known for producing calcitonin, a hormone involved in calcium homeostasis with hypocalcemic and hypophosphatemic effects. Classically, the main endocrine activity of this cell population has been believed to be restricted to its roles in serum calcium and bone metabolism. Nonetheless, in the last few years evidence has been accumulating in the literature with regard to local regulatory peptides secreted by C cells, such as somatostatin, ghrelin, thyrotropin releasing hormone or the recently described cocaine- and amphetamine-related transcript, which could modify thyroid function. As thyrotropin is the main hormone controlling the hypothalamic-pituitary-thyroid axis and, accordingly, thyroid function, we have examined the functional expression of the thyrotropin receptor in C-cell lines and in thyroid tissues. We have found that rat and human C-cell lines express the thyrotropin receptor at both mRNA and protein levels. Furthermore, incubation of C cells with thyrotropin resulted in a 10-fold inhibition of thyrotropin-receptor expression, and a concomitant decrease of the steady-state mRNA levels for calcitonin and calcitonin gene-related peptide determined by quantitative real-time PCR was found. Finally, thyrotropin receptor expression by C cells was confirmed at protein level in both normal and pathological thyroid tissues by immunohistochemistry and immunofluorescence. These results confirm that C cells, under regulation by thyrotropin, are involved in the hypothalamic-pituitary-thyroid axis and suggest a putative role in local fine-tuning of follicular cell activity. PMID:19493188

Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

NASA Astrophysics Data System (ADS)

Rigatos, Gerasimos

2016-12-01

It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

The infundibulo-tuberal syndrome caused by craniopharyngiomas: clinicopathological evidence from an historical French cohort (1705-1973).

PubMed

Castro-Dufourny, Inés; Carrasco, Rodrigo; Prieto, Ruth; Barrios, Laura; Pascual, José M

2015-10-01

Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs). A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era. Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001). This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

Regulation of Pituitary Stem Cells by Epithelial to Mesenchymal Transition Events and Signaling Pathways

PubMed Central

Cheung, Leonard Y. M.; Davis, Shannon W.; Brinkmeier, Michelle L.; Camper, Sally A.; Pérez-Millán, María Inés

2017-01-01

The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism. PMID:27650955

Assessment of wastewater treatment plant effluent effects on fish reproduction

EPA Science Inventory

Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined t...

Bovine temperament impacts immunity, metabolism, and reproduction: A review

USDA-ARS?s Scientific Manuscript database

Temperament, or excitability, is a behavioral trait that has been shown to impact physiology and performance. Temperament in cattle alters the function of the hypothalamic-pituitary-adrenal axis, thereby influencing circulating concentrations of catecholamines and glucocorticoids. The physiological ...

Synthesis of DNA in oestrogen-induced pituitary tumurs in rats: effect of bromocriptine.

PubMed

Kalbermann, L E; Machiavelli, G A; De Nicola, A F; Weissenberg, L S; Burdman, J A

1980-11-01

Bromocriptine increased the concentration of prolactin in oestrogen-induced tumours of the rat pituitary gland. Prolactinaemia was significantly reduced and at the same time there was a considerable decrease in the weight of the tumour, in the incorporation of tritiated thymidine into DNA and in the activity of DNA polymerase alpha. The results suggested that the intracellular content of prolactin controls cell proliferation in this experimental tumour. A hypothalamic disorder is proposed as the primary cause of these tumours.

Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

PubMed

De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

2012-10-01

Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Validation of a Fish Short-term Reproduction Assay

EPA Science Inventory

The Fish Short-term Reproduction Assay is an in vivo assay conducted with fathead minnows and is designed to detect changes in spawning, gross morphology, histopathology, and specific biochemical endpoints that reflect disturbances in the hypothalamic-pituitary-gonadal (HPG) axis...

METABOLOMIC STUDIES OF ENDOCRINE DISRUPTION IN SMALL FISH MODELS

EPA Science Inventory

Metabolomics is now being widely used to obtain complementary information to genomic and proteomic studies. To better understand temporal, compensatory and dose responses to endocrine-disrupting chemicals (EDCs) within the hypothalamic-pituitary¬gonadal (HPG) axis, we have carrie...

Cross-species Extrapolation of EDC Toxicity: Consequences for Screening Programs

EPA Science Inventory

Many structural and functional aspects of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis are known to be highly conserved, but the full significance of this from a toxicological perspective has received comparatively little attention. High-quality data generated through...

Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

PubMed

Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

2016-02-01

Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder. © 2015 Wiley Periodicals, Inc.

Hypogonadotropic hypogonadism revisited.

PubMed

Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

2013-01-01

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm.

Hypogonadotropic Hypogonadism Revisited

PubMed Central

Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

2013-01-01

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm. PMID:23503957

GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.

PubMed

Chaudhari, Nirja; Dawalbhakta, Mitali; Nampoothiri, Laxmipriya

2018-04-11

GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS. PCOS was induced in rats by oral administration of letrozole (aromatase inhibitor). Following PCOS validation, animals were assessed for gonadotropin levels and their mRNA expression. Neurotrasnmitter status was evaluated by estimating their levels, their metabolism and their receptor expression in hypothalamus, pituitary, hippocampus and frontal cortex of PCOS rat model. We demonstrate that GnRH and LH inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are reduced while glutamate, a major stimulator of GnRH and LH release, is increased in the PCOS condition. Concomitant changes were observed for neurotransmitter metabolising enzymes and their receptors as well. Our results reveal that increased GnRH and LH pulsatility in PCOS condition likely result from the cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in hypothalamic-pituitary centre. This, we hypothesise, is responsible for the depression and anxiety-like mood disorders commonly seen in PCOS women.

Risk-adapted, long-term management in childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L

2017-04-01

This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management. Literature search on Pubmed for paper published after 1994. Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome. It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' by experienced multidisciplinary teams in the context of multicenter trials.

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia.

PubMed

Takahashi, Tsutomu; Zhou, Shi-Yu; Nakamura, Kazue; Tanino, Ryoichiro; Furuichi, Atsushi; Kido, Mikio; Kawasaki, Yasuhiro; Noguchi, Kyo; Seto, Hikaru; Kurachi, Masayoshi; Suzuki, Michio

2011-01-15

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (-1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments. Copyright © 2010 Elsevier Inc. All rights reserved.

Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

PubMed

Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

2004-07-01

Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

PubMed

Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2011-01-01

Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

Neutral Sphingomyelinase (SMPD3) Deficiency Causes a Novel Form of Chondrodysplasia and Dwarfism That Is Rescued by Col2A1-Driven smpd3 Transgene Expression

PubMed Central

Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

2007-01-01

Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3−/− mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3−/− mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia. PMID:17591962

Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression.

PubMed

Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

2007-07-01

Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3(-/-) mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3(-/-) mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia.

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes.

PubMed

Child, Christopher J; Blum, Werner F; Deal, Cheri; Zimmermann, Alan G; Quigley, Charmian A; Drop, Stenvert L S; Cutler, Gordon B; Rosenfeld, Ron G

2016-05-01

To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD. © 2016 European Society of Endocrinology.

Emotional Regulation and Depression: A Potential Mediator between Heart and Mind

PubMed Central

Van Gordon, William

2014-01-01

A narrative review of the major evidence concerning the relationship between emotional regulation and depression was conducted. The literature demonstrates a mediating role of emotional regulation in the development of depression and physical illness. Literature suggests in fact that the employment of adaptive emotional regulation strategies (e.g., reappraisal) causes a reduction of stress-elicited emotions leading to physical disorders. Conversely, dysfunctional emotional regulation strategies and, in particular, rumination and emotion suppression appear to be influential in the pathogenesis of depression and physiological disease. More specifically, the evidence suggests that depression and rumination affect both cognitive (e.g., impaired ability to process negative information) and neurobiological mechanisms (e.g., hypothalamic pituitary adrenal axis overactivation and higher rates of cortisol production). Understanding the factors that govern the variety of health outcomes that different people experience following exposure to stress has important implications for the development of effective emotion-regulation interventional approaches (e.g., mindfulness-based therapy, emotion-focused therapy, and emotion regulation therapy). PMID:25050177

Depression and Heart Diseases: Leading Health Problems.

PubMed

Raič, Matea

2017-12-01

Depression is the most common psychiatric disorder in the world population and the most frequent mental disorder in a primary health care. Unrecognized and untreated depression is associated with a poor outcome of treated chronic diseases which co-exist with depression. Depression and cardiovascular diseases are bidirectional related conditions, risks are for each other, and they often co-exist. Depression is a common disorder in cardiovascular patients with a prevalence of 20% to 45%, which is much more frequent than in the general population. In cardiac patients with acute myocardial infarction, depression occurs three times more often than in the general population. Depression has a direct effect on the pathophysiological changes of various organ systems, changing the values of blood pressure, heart rate, vasomotor tone, vascular resistance, blood viscosity and plasma volume. The potential mechanism for developing heart disease in depressed patients includes hypothalamic-pituitary-adrenal gland dysfunction, increased proinflammatory and prothrombotic factor activity, reduced omega-3 fatty acids, reduced heart rate variability, smoking, physical inactivity, reduced mood, self-esteem and self-efficacy.

Towards an Integrated View of Early Molecular Changes Underlying Vulnerability to Social Stress in Psychosis.

PubMed

Barron, Henry; Hafizi, Sina; Mizrahi, Romina

2017-01-01

Psychotic disorders are heterogeneous and complex, involving many putative causal factors interacting along the course of disease development. Many of the factors implicated in the pathogenesis of psychosis also appear to be involved in disease onset and subsequent neuroprogression. Herein, we highlight the pertinent literature implicating inflammation and oxidative stress in the pathogenesis of psychosis, and the potential contribution of N-methyl-D-aspartate receptors (NMDARs). We also emphasize the role of peripubertal social stress in psychosis, and the ways in which hippocampal dysfunction can mediate dysregulation of the hypothalamic-pituitary-adrenal axis and cortisol release. Finally, we propose a model wherein inflammation and oxidative stress act as a first hit, producing altered parvalbumin interneuron development, NMDAR hypofunction, microglial priming, and sensitivity to a second hit of peripubertal social stress. With a greater understanding of how these factors interact, it may be possible to detect, prevent, and treat psychosis more effectively. © 2017 S. Karger AG, Basel.

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

Diagnosis of adrenal failure in critically ill patients.

PubMed

Moraes, Rafael Barberena; Czepielewski, Mauro A; Friedman, Gilberto; Borba, Evandro Lucas de

2011-06-01

In the last two decades there was important evolution on the knowledge of the function of the hypothalamic-pituitary-adrenal axis. In the last decade, the expression "relative adrenal insufficiency" (RAI) was created, and more recently "critical illness-related corticosteroid insufficiency" (CIRCI) was used to designate those patients in which cortisol production was not sufficiently increased in stress situations. Patients with CIRCI have elevated hospital morbidity and mortality. Currently, there is a wide discussion about diagnostic criteria for this dysfunction. Besides basal cortisol, some publications now study the role of other tests, such as cortrosyn test - either in low (1 μg) or high doses (250 μg); free cortisol, salivary cortisol, metyrapone test and others. With this review, we aimed at summarizing the results of the most influent papers that intended to define diagnostic criteria for CIRCI. We also suggest an approach for CIRCI diagnosis and make it clear that the decision about steroid therapy in septic shock patients is matter apart from RAI.

The impact of drugs on male fertility: a review.

PubMed

Semet, M; Paci, M; Saïas-Magnan, J; Metzler-Guillemain, C; Boissier, R; Lejeune, H; Perrin, J

2017-07-01

Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed. © 2017 American Society of Andrology and European Academy of Andrology.

[The treatment of hypogonadism and maintenance of fertility in men].

PubMed

Rabijewski, Michał

2016-03-01

In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis. © 2016 MEDPRESS.

Cushing's disease in a young woman with anorexia nervosa: pathophysiological implications.

PubMed

Katz, J L; Weiner, H; Kream, J; Zumoff, B

1986-12-01

This report describes a 17-year old student who was found to have Cushing's syndrome two years after she had developed anorexia nervosa (AN). The Cushing's syndrome was treated with bilateral resection of enlarged, hyperplastic, non-tumorous adrenal glands. The diagnosis was further confirmed four years later when, two to three years after new symptoms had appeared, an ACTH secreting pituitary adenoma (that is, Cushing's disease) was found on surgery. The possible mechanism for the development of Cushing's disease in a patient with prior anorexia nervosa, a sequence of events reported once previously, is discussed. It is suggested that increased hypothalamic-pituitary corticotroph stimulation in association with the anorexia nervosa, a now well-established endocrine phenomenon, activated an occult, inactive pituitary basophil adenoma in this patient, eventually resulting in autonomous pituitary overproduction of ACTH by the tumor.

In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability.

PubMed

Quinteros, Fernanda A; Poliandri, Ariel H B; Machiavelli, Leticia I; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-01-01

Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function.

USE OF THE LABORATORY RAT AS A MODEL IN ENDOCRINE DISRUPTOR SCREENING AND TESTING

EPA Science Inventory

The screening and testing program the US Environmental Protection Agency is currently developing to detect endocrine-disrupting chemicals (EDCs) is described. EDCs have been shown to alter the following activities: hypothalamic-pituitary-gonadal [HPG] function; estrogen, androge...

Inhibition of the Thyroid Hormone Pathway in Xenopus by Mercaptobenzothiazole

EPA Science Inventory

Amphibian metamorphosis is a thyroid hormone-dependent process that provides a potential model system to assess chemicals for their ability to disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Several studies have demonstrated the sensitivity of this system to a variety of ...

SIGNIFICANCE OF EXPERIMENTAL STUDIES FOR ASSESSING ADVERSE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS

EPA Science Inventory

The U.S. Environmental Protection Agency (US EPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce andr...

Adrenergic and steroid hormone modulation of ozone-induced pulmonary injury and inflammation

EPA Science Inventory

Rationale: We have shown that acute ozone inhalation promotes activation of the sympathetic and hypothalamic-pituitary-adrenal (HPA) axis leading to release of cortisol and epinephrine from the adrenals. Adrenalectomy (ADREX) inhibits ozone-induced pulmonary vascular leakage and ...

Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow

EPA Science Inventory

Gamma aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic pituitary gonadal (HPG) axis, leading to imp...

SMALL FISH MODELS FOR IDENTIFYING AND ASSESSING THE EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Endocrine-disrupting chemicals (EDCs), in particular those which affect the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates, have become a focus of regulatory screening and testing throughout the world. Small fish species, principally the fathead minnow (Pimephales prom...

Dynamic Nature of Alterations in the Endocrine System of Fathead Minnows Exposed to Prochloraz

EPA Science Inventory

The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is controlled through various feedback mechanisms, ideally maintaining dynamic homeostasis in the face of changing environmental conditions, including exposure to chemical stressors. These studies assessed the effects of t...

DISTRIBUTION OF ATRAZINE IN PC12 CELLS AND MODULATION OF CATECHOLAMINE SYNTHESIS

EPA Science Inventory

Previously, we reported that atrazine disrupts ovarian function by altering hypothalamic catecholamine (CA) concentrations and the consequent regulation of pituitary LH release and prolactin secretion in the young female rat. We also showed that atrazine directly interacts with t...

Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment

PubMed Central

2012-01-01

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS. PMID:22844316

Effect of functionally significant deiodinase single nucleotide polymorphisms on drinking behavior in alcohol dependence: an exploratory investigation

PubMed Central

Lee, MR; Schwandt, ML; Bollinger, JW; Dias, AA; Oot, EN; Goldman, D; Hodgkinson, CA; Leggio, L

2016-01-01

Background Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism, however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence (AD). The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes D1, D2 and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNP’s) of these deiodinase genes may play a role in HPT dysfunction. Methods The present study explored the effect of three functionally significant SNP’s (D1: rs2235544, D2: rs225014 and rs12885300) of deiodinase genes on drinking behavior and thyroid stimulating hormone (TSH) levels in alcohol dependent (N=521) and control subjects (N=228). Results Rs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by the Timeline Follow-Back (TLFB). Alcohol-dependent subjects had significantly higher thyroid stimulating hormone levels compared to controls; however, there was no effect of genotype on TSH levels for either group. Conclusions These findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol drinking behavior. PMID:26207529

Impact of N-acetylcysteine and sesame oil on lipid metabolism and hypothalamic-pituitary-adrenal axis homeostasis in middle-aged hypercholesterolemic mice

PubMed Central

Korou, Laskarina-Maria; Agrogiannis, George; Koros, Christos; Kitraki, Efthimia; Vlachos, Ioannis S.; Tzanetakou, Irene; Karatzas, Theodore; Pergialiotis, Vasilios; Dimitroulis, Dimitrios; Perrea, Despina N.

2014-01-01

Hyperlipidemia and stress are important factors affecting cardiovascular health in middle-aged individuals. We investigated the effects of N-acetylcysteine (NAC) and sesame oil on the lipidemic status, liver architecture and the hypothalamic-pituitary-adrenal (HPA) axis of middle-aged mice fed a cholesterol-enriched diet. We randomized 36 middle-aged C57bl/6 mice into 6 groups: a control group, a cholesterol/cholic acid diet group, a cholesterol/cholic acid diet group with NAC supplementation, a cholesterol/cholic acid diet enriched with 10% sesame oil and two groups receiving a control diet enriched with NAC or sesame oil. NAC administration prevented the onset of the disturbed lipid profile, exhibiting decreased lipid peroxidation and alkaline phosphatase (ALP) levels, restored nitric oxide bioavailability and reduced hepatic damage, compared to non-supplemented groups. High-cholesterol feeding resulted in increased hypothalamic glucocorticoid receptors (GR) levels, while NAC supplementation prevented this effect. NAC supplementation presented significant antioxidant capacity by means of preventing serum lipid status alterations, hepatic damage, and HPA axis disturbance due to high-cholesterol feeding in middle-aged mice. These findings suggest a beneficial preventive action of plant-derived antioxidants, such as NAC, on lipid metabolism and on the HPA axis. PMID:25348324

Hypothalamic pathogenesis of type 2 diabetes.

PubMed

Koshiyama, Hiroyuki; Hamamoto, Yoshiyuki; Honjo, Sachiko; Wada, Yoshiharu; Lkeda, Hiroki

2006-01-01

There have recently been increasing experimental and clinical evidences suggesting that hypothalamic dysregulation may be one of the underlying mechanisms of abnormal glucose metabolism. First, increased hypothalamic-pituitary-adrenal axis activity induced by uncontrollable excess stress may cause diabetes mellitus as well as dyslipidemia, visceral obesity, and osteoporosis with some resemblance to Cushing's disease. Second, several molecules are known to be expressed both in pancreas and hypothalamus; adenosine triphosphate-sensitive potassium channels, malonyl-CoA, glucokinase, and AMP-activated protein kinase. Those molecules appear to form an integrated hypothalamic system, which may sense hypothalamic fuel status, especially glucose level, and inhibit action of insulin on hepatic gluconeogenesis, thereby forming a brain-liver circuit. Third, hypothalamic resistance to insulin as an adiposity signal may be involved in pathogenesis of peripheral insulin resistance. The results with mice with a neuron-specific disruption of the insulin receptor gene or those lacking insulin receptor substrate 2 in hypothalamus supported this possibility. Finally, it has very recently been suggested that dysregulation of clock genes in hypothalamus may cause abnormal glucose metabolism. Taken together, it is plausible that some hypothalamic abnormality may underlie at least some portion of type 2 diabetes or insulin resistance in humans, and this viewpoint of hypothalamic pathogenesis of type 2 diabetes may lead to the development of new drugs for type 2 diabetes.

Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

PubMed

Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

2008-09-01

Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

Adverse Effects of Two Nights of Sleep Restriction on the Hypothalamic-Pituitary-Adrenal Axis in Healthy Men

PubMed Central

Guyon, A.; Balbo, M.; Morselli, L. L.; Tasali, E.; Leproult, R.; L'Hermite-Balériaux, M.; Van Cauter, E.

2014-01-01

Context: Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. Objective: Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. Methods: Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. Results: Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (−21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. Conclusion: The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks. PMID:24823456

Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

PubMed

Guyon, A; Balbo, M; Morselli, L L; Tasali, E; Leproult, R; L'Hermite-Balériaux, M; Van Cauter, E; Spiegel, K

2014-08-01

Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

Approaches Mediating Oxytocin Regulation of the Immune System.

PubMed

Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

2016-01-01

The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

PubMed

Lapp, Hannah E; Ahmed, Sarah; Moore, Celia L; Hunter, Richard G

2018-02-21

Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cocchi, Daniela; Tulipano, Giovanni; Colciago, Alessandra

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy frommore » GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.« less

Excess Testosterone Exposure Alters Hypothalamic-Pituitary-Testicular Axis Dynamics and Gene Expression in Sheep Fetuses

PubMed Central

Amodei, Rebecka; Gribbin, Kyle P.; Corder, Keely; Stormshak, Fred; Estill, Charles T.

2016-01-01

Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunit mRNA in both sexes and the levels of GnRH receptor mRNA in males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reduced mRNA levels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P < .01) in control females than in males and reduced (P < .001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor-β, and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life. PMID:27673555

Effect of SKI2670, a novel, orally active, non-peptide GnRH antagonist, on hypothalamic-pituitary-gonadal axis.

PubMed

Kim, Seon Mi; Yoo, Taekyung; Lee, So Young; Kim, Eun Jeong; Lee, Soo Min; Lee, Min Hee; Han, Min Young; Jung, Seung-Hyun; Choi, Jung-Hye; Ryu, Keun Ho; Kim, Hun-Taek

2015-10-15

Suppression of the hypothalamic-pituitary-gonadal axis has been widely utilized for the management of gonadal-hormone-dependent diseases such as endometriosis. Efforts to develop orally available gonadotropin-releasing hormone (GnRH) antagonists for the treatment of gonadal-hormone-dependent diseases led to the discovery of SKI2670, a novel non-peptide GnRH antagonist. The present study was undertaken to pharmacologically characterize SKI2670 in vitro and in vivo. We measured binding affinity and antagonistic activity of SKI2670 for the GnRH receptors. Immediate suppression of gonadotropins by single dosing of SKI2670 was examined in castrated monkeys. Subsequently, influence on gonadal hormones by prolonged administration of SKI2670 was assessed in naive female monkeys. To investigate in vivo efficacy of SKI2670, regression of ectopic implants by repeated administration of SKI2670 was examined in a rat endometriosis model. SKI2670 is a potent functional antagonist for the human GnRH receptor, with subnanomolar binding affinity. In castrated monkeys, single administration of SKI2670 lowered serum luteinizing hormone (LH) levels stronger with longer duration when compared to elagolix at equivalent doses. Moreover, repeated dosing of SKI2670 suppressed serum levels of gonadotropins and gonadal hormones in intact female monkeys while elagolix suppressed serum LH levels only. Finally, it exhibited regressive effects on ectopic implants in a rat endometriosis model without bone loss. Our findings demonstrate robust GnRH antagonistic efficacy of SKI2670 in animal models, suggesting that SKI2670-induced suppression of the hypothalamic-pituitary-gonadal axis may be beneficial for the treatment of gonadal-hormone-dependent diseases such as endometriosis in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

PubMed

Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

2017-10-01

Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T 3 ) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

Individual and Day-to-Day Differences in Active Coping Predict Diurnal Cortisol Patterns among Early Adolescent Girls.

PubMed

Sladek, Michael R; Doane, Leah D; Stroud, Catherine B

2017-01-01

Prior work has identified alterations in activity of the hypothalamic-pituitary-adrenal axis as a potential mechanism underlying stress-induced emotional health problems, which disproportionately impact girls beginning in mid-adolescence. How adolescent girls differ from one another in dispositional coping tendencies and shift specific coping strategies in response to varying stressors have been theorized as important predictors of their adaptation, health, and well-being during this dynamic period of development. The goal of this study was to examine whether individual and day-to-day (within-person) differences in adolescent girls' coping responses are associated with daily patterns of hypothalamic-pituitary-adrenal axis activity, indexed by cortisol. Participants were 122 early adolescent girls (M age  = 12.39) who provided three saliva samples per day for 3 days and completed daily coping reports, as well as a standard coping survey. Participants and primary caregivers also completed objective life stress interviews. On average, girls who were more likely to respond to interpersonal stress with voluntary engagement (active) coping exhibited generally adaptive daily physiological regulation-steeper diurnal cortisol slopes, lower total diurnal cortisol output, and lower cortisol awakening responses. Chronic interpersonal stress level significantly moderated these associations in different ways for two distinct components of the diurnal pattern-the slope and cortisol awakening responses. Regarding within-person differences, using active coping more than usual was associated with higher waking cortisol the following morning, which may help to prepare adolescent girls for perceived daily demands. These findings highlight the interactive influence of stress and coping in the prediction of daily hypothalamic-pituitary-adrenal axis activity and support the stress-buffering role of active coping for adolescent girls.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

PubMed Central

Michailidou, Z.; Carter, R. N.; Marshall, E.; Sutherland, H. G.; Brownstein, D. G.; Owen, E.; Cockett, K.; Kelly, V.; Ramage, L.; Al-Dujaili, E. A. S.; Ross, M.; Maraki, I.; Newton, K.; Holmes, M. C.; Seckl, J. R.; Morton, N. M.; Kenyon, C. J.; Chapman, K. E.

2008-01-01

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GRβgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.—Michailidou, Z., Carter, R. N., Marshall, E., Sutherland, H. G., Brownstein, D. G., Owen, E., Cockett, K., Kelly, V., Ramage, L., Al-Dujaili, E. A. S., Ross, M., Maraki, I., Newton, K., Holmes, M. C., Seckl, J. R., Morton, N. M., Kenyon, C. J., Chapman, K. E. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. PMID:18697839

Diurnal cortisol rhythms among Latino immigrants in Oregon, USA

PubMed Central

2012-01-01

One of the most commonly used stress biomarkers is cortisol, a glucocorticoid hormone released by the adrenal glands that is central to the physiological stress response. Free cortisol can be measured in saliva and has been the biomarker of choice in stress studies measuring the function of the hypothalamic-pituitary-adrenal axis. Chronic psychosocial stress can lead to dysregulation of hypothalamic-pituitary-adrenal axis function and results in an abnormal diurnal cortisol profile. Little is known about objectively measured stress and health in Latino populations in the United States, yet this is likely an important factor in understanding health disparities that exist between Latinos and whites. The present study was designed to measure cortisol profiles among Latino immigrant farmworkers in Oregon (USA), and to compare quantitative and qualitative measures of stress in this population. Our results indicate that there were no sex differences in average cortisol AUCg (area under the curve with respect to the ground) over two days (AvgAUCg; males = 1.38, females = 1.60; P = 0.415). AUCg1 (Day 1 AUCg) and AvgAUCg were significantly negatively associated with age in men (P<0.05). AUCg1 was negatively associated with weight (P<0.05), waist circumference (P<0.01) and waist-to-stature ratio (P<0.05) in women, which is opposite of the expected relationship between cortisol and waist-to-stature ratio, possibly indicating hypothalamic-pituitary-adrenal axis dysregulation. Among men, more time in the United States and immigration to the United States at older ages predicted greater AvgAUCg. Among women, higher lifestyle incongruity was significantly related to greater AvgAUCg. Although preliminary, these results suggest that chronic psychosocial stress plays an important role in health risk in this population. PMID:22738123

Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

PubMed

Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

2016-01-01

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in diabetes mellitus-associated late-onset hypogonadism. © Georg Thieme Verlag KG Stuttgart · New York.

HYPOTHALAMIC DIGOXIN AND SCHIZOPHRENIA - A MODEL FOR CONSCIOUS AND SUBLIMINAL PERCEPTION AND ITS DYSFUNCTION IN SCHIZOPHRENIA

PubMed Central

Kurup, Ravikumar A.; Augustine, Jyothi; Kurup, P.A.

1999-01-01

In view of reports of an upregulated cation pump in genetically related Bipolar Affective Disorders the role of hypothalamic digoxin, an endogenous regulator of the cation pump was studied with special reference to its role as a modulator of glycoprotein synthesis. The study demonstrated elevated serum digoxin levels, elevated HMG CoA reductase activity suggesting increased digoxin synthesis, reduced sodium-potassium ATPase activity and altered sugar residues of serum glycoprotein in schizophrenia. A hypothalamic digoxin mediated model for conscious and subliminal perception is proposed and the significance of its dysfunction due to abnormal glycoprotein induced synaptic connectivity defects in schizophrenia is discussed. PMID:21455390

Hormonal changes in humans during spaceflight.

PubMed

Strollo, F

1999-01-01

Readers of this review may feel that there is much more that we do not know about space endocrinology than what we know. Several reasons for this state of affairs have been given: 1. the complexity of the field of endocrinology with its still increasing number of known hormones, releasing factors and precursors, and of the interactions between them through various feedback mechanisms 2. the difficulty in separating the microgravity effects from the effects of stress from launch, isolation and confinement during flight, reentry, and postflight re-adaptation 3. the experimental limitations during flight, such as limited number of subjects, limited number of samples, impossibility of collecting triple samples for pulsatile hormones like growth hormone 4. the disturbing effects of countermeasures used by astronauts 5. the inadequacy of postflight samples for conclusions about inflight values 6. limitations of conclusions from animal experiments and space simulation studies The endocrinology field is divided in to nine systems or axes, which are successively reviewed: 1. Rapid bone demineralization in the early phase of spaceflight that, when unopposed, leads to catastrophic effects after three months but that slows down later. The endocrine mechanism, apart from the effect of exercise as a countermeasure, is not yet understood. 2. The hypothalamic-pituitary-adrenal axis is involved in stress reactions, which complicate our understanding and makes postflight analysis dubious. 3. In the hypothalamic-pituitary-gonadal axis, pulsatility poses a problem for obtaining representative values (e.g., for luteinizing hormone). Reproduction of rats in space is possible, but much more needs to be known about this aspect, particularly in women, before the advent of space colonies, but also in males because some evidence for reversible testicular dysfunction in space has been found. 4. The hypothalamic-pituitary-somato-mammotrophic axis involves prolactin and growth hormone. The latter also acts as a stress hormone and its secretion is greatly decreased in spaceflown rats, but not in astronauts, which may be due to differences in the regulation of growth hormone secretion between rats and humans. 5. The hypothalamic-pituitary-thyroid axis involves the thyroid hormones thyroxine and triiodothyronine, which are lowered in space, suggesting mild hypothyroidism. 6. The renin-angiotensin-aldosterone axis, which regulates water and electrolytes, involves antidiuretic hormone and two natriuretic peptides and shows paradoxical behavior in space. 7. Erythrocyte mass regulation involves erythropoietin, and space anemia is still not explained. 8. The endocrine pancreas involves insulin and glucagon, with loss of insulin sensitivity in space due to lack of exercise, which phenomenon requires more study before the advent of space colonies. 9. The sympathetic system acts through epinephrine, norepinephrine and dopamine and seems to have an increased activity in space in contrast to what had been widely believed. From the foregoing conclusions, it is clear that much further study is needed in all fields of space endocrinology. On the other hand, future studies will allow us to understand what happens in a given endocrine subsystem in the absence of the "gravity factor", the perturbing factor to which the human race has become adapted through thousands of years of evolution. This should provide us with a fuller understanding of the internal homeostatic mechanisms. An important point is that some endocrine systems seem to undergo changes in space that resemble those observed during senescence, but after spaceflight, recovery always occurs within weeks or months after return. This is particularly true for the systems regulating bone and muscle metabolism and reproduction, exactly as happens with the immune, neurosensory, and cardiovascular systems. Further space research may help us find new insights in the pathophysiology of aging and hopefully define novel prev

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

Stress during pregnancy alters the offspring hypothalamic, pituitary, adrenal, and testicular response to isolation on the day of weaning.

PubMed

Williams, M T; Davis, H N; McCrea, A E; Hennessy, M B

1999-01-01

Subjecting pregnant female rats to situations that activate the hypothalamic-pituitary-adrenal (HPA) axis can have long-term effects on the development of the offspring. Restraint under bright lights is a common method of stressing pregnant females that results in consistent behavioral changes in the offspring. We investigated the effects of gestationally administered restraint, bright lights, and heat on the HPA axis response of 21-day-old offspring following exposure to isolation in a novel environment or under resting conditions. Corticotropin-releasing factor titers in the hypothalamus were unaffected following isolation. Nonetheless, adrenocorticotropin hormone (ACTH) was found to be lower in the gestationally stressed offspring prior to or following the isolation period. Corticosterone was attenuated in gestationally stressed offspring following the postnatal stressor and there was also a tendency for the gestationally stressed females to have lower concentrations of aldosterone. Plasmatic testosterone levels were higher in the gestationally stressed males following the period of isolation. The present data suggest that the HPA axis of the offspring is differentially affected by the gestational stress procedure, that is, it is attenuated at the level of the pituitary and adrenal, but not at the level of the hypothalamus. These data have implications for behavioral differences observed in gestationally stressed animals.

Erratum to "CNS drugs in Cushing's disease: pathophysiological and therapeutic implications for mood disorders" [Prog. Neuro-Psycol. Biol. Psychiatry, 26, 763 (2002)].

PubMed

Sonino, Nicoletta; Fava, Giovanni A

2002-06-01

Cushing's syndrome is due to chronic glucocorticoid excess that may have various etiologies. The most common endogenous form is pituitary-dependent bilateral adrenal hyperplasia, which is termed Cushing's disease. Major depression occurs in more than half of the cases. The presence of depressive symptoms connotes severity of clinical presentation and, in patients with hypothalamic-pituitary forms, entails prognostic value. Medical treatment may be used while awaiting more definitive solutions for the illness by surgery. The inhibitors of steroid production (e.g., ketoconazole, metyrapone and aminoglutethimide), rather than antidepressant drugs, are generally successful in lifting depression as well as other disabling symptoms. Since central serotonergic regulation could have a role in the course of Cushing's disease, serotonin antagonists (e.g., cyproheptadine, ritanserin and ketanserin) have been employed. Findings related to the pharmacological response of depression in Cushing's disease were found to have implications for the pathophysiology of depression and the potential involvement of the hypothalamic-pituitary-adrenal axis (HPA axis) in resistance and tolerance to antidepressant drugs. The use of serotonergic drugs in Cushing's disease may yield important insights in the understanding of serotonergic regulation both in Cushing's disease and in the HPA axis in nonendocrine major depression.

Effects of Environmentally Relevant Concentrations of Bisphenol A on the Fathead Minnow

EPA Science Inventory

Bisphenol A (BPA) is a wide-spread environmental contaminant of concern due, in part, to possible effects on the vertebrate hypothalamic-pituitary-gonadal (HPG) axis, including activation of the estrogen receptor (ER). There is a reasonable amount of toxicological information fo...

Evaluating the involvement of glucocorticoid feedback on the reproductive effects of environmental chemicals

EPA Science Inventory

Acute and chronic stressors activate the hypothalamic-pituitary-adrenal (lIPA) axis and are known to suppress reproductive function through central negative feedback of the gonadal axis by glucocorticoids. Recently, several environmental chemicals known to attenuate or suppress t...

Chlorotriazine Herbicides and Metabolites Activate an ACTH-Dependent Release of Corticosterone in Male Wistar Rats

EPA Science Inventory

Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in elevated serum corticosterone (CORT), progesterone, and estrogens. The increase in CORT indicated that this chlorotriazine herbicide may alter the hypothalamic-pituitary-adrenal ax...

STRATEGIES TO REDUCE OR REPLACE THE USE OF ANIMALS IN THE ENDOCRINE SCREENING AND TESTING PROGRAM.

EPA Science Inventory

Abstract: The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen and thyroid hormone synthesis and androgen (AR...

Social hierarchy modulates responses of fish exposed to contaminants of emerging concern

EPA Science Inventory

Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circul...

Thyroid Histopathology Assessments for the Amphibian Metamorphosis Assay to Detect Thyroid-active Substances

EPA Science Inventory

In support of an Organization for Economic Cooperation and Development (OECD) Amphibian Metamorphosis Assay (AMA) Test Guideline for the detection of substances that interact with the hypothalamic-pituitary-thyroid axis, a document was developed that provides a standardized appro...

Fetal and postnatal nutritional programming of reproductive performance in ruminants

USDA-ARS?s Scientific Manuscript database

The influence of nutrition on reproductive function in females has been studied for decades. In cows, early studies focused on the influence of nutritional status on the hypothalamic-pituitary-ovarian axis, demonstrating that in circumstances of extreme negative energy balance estrous cycles cease....

Maternal Influences on Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis

EPA Science Inventory

Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing risk of disease later in life. Underlying mechanisms are beginning to be elucidated, and effects on a number of organ...

Adrenocortical Activity and Emotion Regulation.

ERIC Educational Resources Information Center

Stansbury, Kathy; Gunnar, Megan R.

1994-01-01

This essay argues that the activity of the hypothalamic-pituitary-adrenocortical (HPA) system does not appear to be related to emotion regulation processes in children, although individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally…

ATRAZINE DISRUPTS THE HYPOTHALAMIC CONTROL OF PITUITARY-OVARIAN FUNCTION

EPA Science Inventory

The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) constitute the largest group of herbicides sold in the United States. Despite their extensive usage, relatively little is known about the possible human-health effects and mechanism(s) of action of these compo...

Investigation of adaptive responses in fathead minnows (Pimephales promelas) exposed to the model aromatase inhibitor fadrozole

EPA Science Inventory

The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is a highly dynamic system, which, through various feedback mechanisms, strives to maintain physiological conditions conducive to reproduction even in potentially stressful situations. The development of useful predictive m...

Adaptation to chemical perturbation in the HPG axis: Implications for assessment and monitoring

EPA Science Inventory

Over the past 15 years chemicals that impact the vertebrate hypothalamic-pituitary-gonadal (HPG) axis have arguably received more attention relative to research and regulation than any other class of environmental contaminants. Testing and monitoring programs to identify and ass...

Simultaneous analysis of thirteen endogenous steroid hormones by liquid chromatography tandem mass spectrometry with atmospheric pressure photoionization

EPA Science Inventory

Exposure to endocrine active chemicals can lead to perturbations of the hypothalamic-pituitary-gonadal (HPG) axis, ultimately leading to adverse reproductive effects. To evaluate potential reproductive effects, many aquatic toxicity assessments still rely on radioimmunoassay (RIA...

Ginseng and the hypothalamic-pituitary control of stress.

PubMed

Fulder, S J

1981-01-01

There are a group of so-called tonic remedies in Far Eastern medicine which are traditionally viewed as harmonizing or adjustive. Ginseng and eleutherococcus are the best known, and there is evidence that they increase arousal, stamina and stress resistance. We have attempted to explore the relationship between the behavioral and the stress effects, and to relate this to traditional concepts. In one series of experiments mice were given ginseng throughout their lifespan. At intervals their behavior response to mild stress was examined and found to be exaggerated compared to controls without ginseng. However, normal ambulatory behavior in the absence of stress was unaffected. A second series of experiments indicated that the binding of corticosteroid to certain brain regions was increased in adrenalectomized rats given ginseng saponin, compared to saline treated controls. This can be interpreted as a result of an increase in hypothalamic-pituitary-adrenal sensitivity caused by ginseng saponin. This is in accord with traditional concepts of the use of these remedies.

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic-Pituitary-Adrenal Axis.

PubMed

Borrow, A P; Stranahan, A M; Suchecki, D; Yunes, R

2016-07-01

The central nervous system regulates and responds to endocrine signals, and this reciprocal relationship determines emotional processing and behavioural anxiety. Although the hypothalamic-pituitary-adrenal (HPA) axis remains the best-characterised system for this relationship, other steroid and peptide hormones are increasingly recognised for their effects on anxiety-like behaviour and reward. The present review examines recent developments related to the role of a number of different hormones in anxiety, including pregnane neurosteroids, gut peptides, neuropeptides and hormonal signals derived from fatty acids. Findings from both basic and clinical studies suggest that these alternative systems may complement or occlude stress-induced changes in anxiety and anxiety-like behaviour. By broadening the scope of mechanisms for depression and anxiety, it may be possible to develop novel strategies to attenuate stress-related psychiatric conditions. The targets for these potential therapies, as discussed in this review, encompass multiple circuits and systems, including those outside of the HPA axis. © 2016 British Society for Neuroendocrinology.

Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

NASA Astrophysics Data System (ADS)

Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

2017-12-01

A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo-Testicular Descent and Maldescent

PubMed Central

Hadziselimovic, Faruk

2016-01-01

Maldescent of the epididymo-testicular unit can occur as an isolated event or as a component of various syndromes. When part of a syndrome, crypto-epididymis is usually accompanied by other genital and/or extragenital features. Epididymis development is primarily regulated by androgens, and successful epididymo-testicular unit development and descent requires an intact hypothalamic-pituitary-gonadal axis. The developing gonadotropin-releasing hormone system is essential for epididymo-testicular descent and is highly sensitive to reduced fibroblast growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the process of epididymo-testicular descent has recently improved. At later stages of embryonic development, the undifferentiated epididymal mesenchyme is a specific domain for FGFR1 expression. The majority of individuals with syndromic crypto-epididymis, as well as individuals with isolated maldescent of the epididymo-testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms underlying FGF dysregulation may differ between various syndromes. PMID:27022326

Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo-Testicular Descent and Maldescent.

PubMed

Hadziselimovic, Faruk

2016-02-01

Maldescent of the epididymo-testicular unit can occur as an isolated event or as a component of various syndromes. When part of a syndrome, crypto-epididymis is usually accompanied by other genital and/or extragenital features. Epididymis development is primarily regulated by androgens, and successful epididymo-testicular unit development and descent requires an intact hypothalamic-pituitary-gonadal axis. The developing gonadotropin-releasing hormone system is essential for epididymo-testicular descent and is highly sensitive to reduced fibroblast growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the process of epididymo-testicular descent has recently improved. At later stages of embryonic development, the undifferentiated epididymal mesenchyme is a specific domain for FGFR1 expression. The majority of individuals with syndromic crypto-epididymis, as well as individuals with isolated maldescent of the epididymo-testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms underlying FGF dysregulation may differ between various syndromes.

Seasonal and sex-related variations in serum steroid hormone levels in wild and farmed brown trout Salmo trutta L. in the north-west of Spain.

PubMed

Fregeneda-Grandes, Juan M; Hernández-Navarro, Salvador; Fernandez-Coppel, Ignacio A; Correa-Guimaraes, Adriana; Ruíz-Potosme, Norlan; Navas-Gracia, Luis M; Aller-Gancedo, J Miguel; Martín-Gil, Francisco J; Martín-Gil, Jesús

2013-12-01

Serum steroid profiles were investigated in order to evaluate the potential use of circulating sex steroid levels as a tool for sex identification in brown trout. Changes in the serum concentrations of testosterone (T), progesterone (P), 17-β-estradiol (E2), and cortisol (F) in wild and farmed mature female and male brown trout, Salmo trutta L., were measured in each season (January, May, July, and October) in six rivers and four hatcheries located in the north-west of Spain. Serum cortisol levels in farmed brown trout were significantly higher and showed a seasonal pattern opposite to that found in wild trout. Because levels of the hormones under study can be affected by disruptive factors such as exposure to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary-adrenal axis), both factors are taken into account.

Impact of food restriction on ovarian development, RFamide-related peptide-3 and the hypothalamic-pituitary-ovarian axis in pre-pubertal ewes.

PubMed

Li, H; Song, H; Huang, M; Nie, H; Wang, Z; Wang, F

2014-10-01

RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, has been implicated as a mediator between reproduction and energy balance. This study aimed to investigate the physiological effects of RFRP-3 on the process of ovarian development in food-restricted pre-pubertal ewes. The results showed that food restriction significantly inhibited the ovarian development and follicular growth. The data of qPCR in the hypothalamic-pituitary-ovarian (HPO) axis showed that food restriction not only upregulated RFRP-3 mRNA expression but also downregulated the mRNA expression of gonadotropin-releasing-hormone receptor, follicle-stimulating hormone receptor and luteinizing hormone receptor (LHR). Immunohistochemistry of RFRP-3 in the ovaries suggested that RFRP-3 may regulate the follicular development. These results suggested that the changes of RFRP-3 in response to food restriction might influence the HPO axis and inhibit ovarian development. © 2014 Blackwell Verlag GmbH.

Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory.

PubMed

McCormick, Cheryl M; Mathews, Iva Z

2010-06-30

Chronic exposure to stress is known to affect learning and memory in adults through the release of glucocorticoid hormones by the hypothalamic-pituitary-adrenal (HPA) axis. In adults, glucocorticoids alter synaptic structure and function in brain regions that express high levels of glucocorticoid receptors and that mediate goal-directed behaviour and learning and memory. In contrast to relatively transient effects of stress on cognitive function in adulthood, exposure to high levels of glucocorticoids in early life can produce enduring changes through substantial remodeling of the developing nervous system. Adolescence is another time of significant brain development and maturation of the HPA axis, thereby providing another opportunity for glucocorticoids to exert programming effects on neurocircuitry involved in learning and memory. These topics are reviewed, as is the emerging research evidence in rodent models highlighting that adolescence may be a period of increased vulnerability compared to adulthood in which exposure to high levels of glucocorticoids results in enduring changes in adult cognitive function. Copyright 2009 Elsevier Inc. All rights reserved.

The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

PubMed

Ikegami, Keisuke; Yoshimura, Takashi

2017-10-01

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review.

PubMed

van Dalfsen, Jens H; Markus, C Rob

2018-06-01

Inadequate sleep is highly prevalent and known to decline both physical- and mental health. Literature suggests that altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association. This assumption is mainly based on changes in basal neuroendocrine activity and it is of equal importance to elucidate whether sleep may also influence HPA stress responsiveness. The present review provides a complete outline of recent human studies that have investigated how different aspects of sleep influence cortisol reactivity to laboratory stress. From the available data it can be concluded that both objective and subjective decrements in sleep quality potentiate the stress reactivity of the HPA axis. On the contrary, normal variations in sleep duration do not seem to influence cortisol stress responsiveness whereas excessive daytime sleepiness is associated with a blunting of the cortisol response. Given its well-established health consequences, sensitization of the HPA axis might well be a crucial component linking inadequate sleep to stress-related pathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans.

PubMed

Gifford, Robert M; Reynolds, Rebecca M

2017-11-01

Increasing evidence supports fetal glucocorticoid exposure with associated altered offspring hypothalamic-pituitary-adrenal (HPA) axis activity as a key mechanism linking early life events with later life disease. Alterations in HPA axis activity are linked to a range of cardiometabolic and psychiatric diseases. As many of these diseases manifest sex differences in presentation we review the evidence for programmed sex-differences in the HPA axis. Available literature suggests vulnerability of the female HPA axis to prenatal stressors with female offspring demonstrating increased HPA axis reactivity. This may be due to changes in placental glucocorticoid metabolism leading to increased fetal glucocorticoid exposure. We discuss the potential consequences of increased vulnerability of the female HPA axis for later life health and consider the underlying mechanisms. Further studies are needed to determine whether sex-differences in early-life programming of the HPA axis represent a pathway underpinning the sex-differences in common cardiometabolic and psychiatric diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Developmental and Contextual Considerations for Adrenal and Gonadal Hormone Functioning During Adolescence: Implications for Adolescent Mental Health

PubMed Central

Ruttle, Paula L.; Shirtcliff, Elizabeth A.; Essex, Marilyn J.; Susman, Elizabeth J.

2014-01-01

Substantial research has implicated the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes independently in adolescent mental health problems, though this literature remains largely inconclusive. Given the cross-talk between the HPA and HPG axes and their increased activation in adolescence, a dual-axis approach that examines both axes simultaneously is proposed to predict the emergence and persistence of adolescent mental health problems. After briefly orienting readers to HPA and HPG axis functioning, we review the literature examining associations between hormone levels and changes with behavior during adolescence. Then, we provide a review of the literature supporting examination of both axes simultaneously and present the limited research that has taken a dual-axis approach. We propose future directions including consideration of between-person and within-person approaches to address questions of correlated changes in HPA and HPG hormones. Potential moderators are considered to increase understanding of the nuanced hormone–behavior associations during key developmental transitions. PMID:24729154

[Etiological diagnosis of central diabetes insipidus: about 41 cases].

PubMed

Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

2016-01-01

The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

Oxytocin in survivors of childhood-onset craniopharyngioma.

PubMed

Daubenbüchel, Anna M M; Hoffmann, Anika; Eveslage, Maria; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Martens, Henri; Geenen, Vincent; Müller, Hermann L

2016-11-01

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

PubMed

Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

2006-04-01

The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper.

PubMed

Li, Shuisheng; Xiao, Ling; Liu, Qiongyu; Zheng, Binbin; Chen, Huapu; Liu, Xiaochun; Zhang, Yong; Lin, Haoran

2015-10-01

Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orange-spotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu- and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhβ) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshβ), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper. © 2015 Society for Endocrinology.

The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that ismore » neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk assessments for AA.« less

Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology.

PubMed

Webb, S M; Ruscalleda, J; Schwarzstein, D; Calaf-Alsina, J; Rovira, A; Matos, G; Puig-Domingo, M; de Leiva, A

1992-05-01

We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

[MR findings in patients with idiopathic panhypopituitarism].

PubMed

Fahrendorf, G; Brämswig, J; Bals-Pratsch, M

1990-05-01

High-resolution MR imaging was performed in seven patients with pituitary dwarfism and panhypopituitarism. In five cases MR-findings included absence of the infundibulum and of the normal intrasellar posterior pituitary bright spot, and the presence of a small nodule at the median eminence. The absence of diabetes insipidus in these patients and the signal characteristics of the nodule at the median eminence suggest that the latter may represent a functioning ectopic posterior pituitary lobe. This complex of findings was only observed in patients with complications in the perinatal period (breech delivery) and appears to be the end result of an ischemic or traumatic injury of the infundibular stem. The infundibular defect would explain both the permanent hormone deficiency of the anterior pituitary gland through a disruption of the hypothalamic-hypophyseal portal system and the absence of diabetes insipidus through an ectopic regeneration of the neurohypophysis at the median eminence.

Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

EPA Science Inventory

Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). These assays can be sensitive ...

Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

EPA Science Inventory

Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

Off-Time Pubertal Timing Predicts Physiological Reactivity to Postpuberty Interpersonal Stress

ERIC Educational Resources Information Center

Smith, Anne Emilie; Powers, Sally I.

2009-01-01

We investigated associations between retrospectively assessed timing of pubertal development, interpersonal interactions, and hypothalamic-pituitary-adrenal axis reactivity to an interpersonal stress task in 110 young adult women. Participants provided salivary cortisol samples at points prior and subsequent to a video-taped conflict discussion…

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

EPA Science Inventory

While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

EPA Science Inventory

While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

A Time-course Study with the Androgen Receptor Antagonist Flutamide in Fish

EPA Science Inventory

Flutamide, a drug registered to treat some types of prostate cancer in humans, has been used for many years as a model androgen receptor (AR) antagonist in studies aimed at characterizing disruption of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis. Various studies hav...

Identification of Gender-specific Transcripts by Microarray in Gonad Tissue of Larval and Juvenile Xenopus tropicalis

EPA Science Inventory

Amphibian model species Xenopus tropicalis is currently being utilized by EPA in the development of a standardized in vivo reproductive toxicity assay. Perturbations to the hypothalamic-pituitary-gonadal axis from exposure to endocrine disrupting compounds during larval develop...

Analysis of thyroid hormones in gland and serum using liquid chromatography-tandem mass spectrometry

EPA Science Inventory

Thyroid hormones (THs), which are critical for growth and development in all vertebrates, can be impacted through chemical perturbation of the hypothalamic-pituitary-thyroid (HPT)-axis. Amphibian and mammalian models are being used to address this research priority within US EPA...

Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

EPA Science Inventory

Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

The Use of MS-based Metabolomics to Determine Markers Associated with Endocrine Disruption in Small Fish Species

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) are exogenous substances that disrupt the physiological function of endogenous hormones. In fish, these xenobiotics are capable of interfering with the dynamic equilibrium of the hypothalamic-pituitary-gonadal (HPG) axis resulting in adverse ...

Short-term effects of propiconazole on hypothalamic-pituitary-gonadal function in the fathead minnows (Pimephales promelas)

EPA Science Inventory

Propiconazole is an ergosterol inhibitor commonly used in agriculture and has been detected in aquatic environments. Ergosterol inhibitors decrease fungal growth through effects on 14á-demethylase, a cytochrome P450 (CYP), isoform important for ergosterol biosynthesis. In higher ...

Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition II: Computational Modeling

EPA Science Inventory

ABSTRACT Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic­ pituitary-gonadal (HPG) axis in female fathead minnows to predic...

Cross-species conservation of endocrine pathways provides a basis for reevaluation of EDSP tiered testing paradigm

EPA Science Inventory

Many structural and functional aspects of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis are known to be highly conserved, but the relative significance of this from a regulatory toxicology perspective has received comparatively little attention. High-quality data gene...

Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain injury.

PubMed

Hari Kumar, K V S; Swamy, M N; Khan, M A

2016-01-01

Traumatic brain injury (TBI) is common in young soldiers of armed forces leading to significant morbidity and mortality. We studied the prevalence of hypopituitarism following TBI and its association with trauma severity. We conducted a 12-month prospective study of 56 TBI patients for the presence of hormonal dysfunction. Hormonal parameters were estimated during the early phase (0-10 days posttraumatically) and after 6 and 12 months. Dynamic testing was done when required, and the results were analyzed by appropriate statistical methods. Hormonal dysfunction was seen in 39 of the 56 (70%) patients at initial assessment. Persisting pituitary deficiencies are seen in 7 and 8 patients at the end of 6 months and 12 months, respectively. Hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency are the most common diagnoses. Initial severe TBI and plurihormonal involvement predicted the long-term hypopituitarism. Early hypopituitarism was common in severe TBI, but recovers in majority. Evaluation for the occult pituitary dysfunction is required during the rehabilitation of TBI patients.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

PubMed

Cuesta, Martín; Hannon, Mark J; Crowley, Rachel K; Behan, Lucy Ann; Tormey, William; Rawluk, Daniel; Delargy, Mark; Agha, Amar; Thompson, Christopher J

2016-01-01

The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P < 0·0001), GT (90% vs 16%, P < 0·0001) deficiency and any pituitary hormone deficit (80% vs 33%, P = 0·003) than G1. Men with symptoms of hypogonadism had more GH (33% vs 11%, P = 0·003), GT (58% vs 16%, P < 0·0001) and TSH (16% vs 1%, P = 0·03) deficiency than G1. Patients with nonspecific symptoms were no more likely to have hypopituitarism than those consecutively screened. Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening. © 2015 John Wiley & Sons Ltd.

Open questions in current models of antidepressant action

PubMed Central

Tanti, A; Belzung, C

2010-01-01

Research on depression and antidepressant drugs is necessary, as many patients display poor response to therapy. Different symptomatic and pathophysiological features have been proposed as end points of the depressive phenotype and of the antidepressant action, including anhedonia, depressed mood, alterations in morphology and activity of some brain areas (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex), modifications in the connectivity between brain structures, changes in neurotransmitters (serotonin, noradrenaline, glutamate and neuropeptides), brain plasticity (neurogenesis, neurotrophins) and abnormal function of the hypothalamic-pituitary adrenal axis. However, few models have been proposed to describe how these end points could induce the depressive phenotype and are involved in the mechanism of action of antidepressants. Here we propose a connectionist-inspired network of depression and antidepressant action, in which the different aetiological factors participating in the release of a depressive episode are represented by input nodes, the different symptomatic as well as pathophysiological end points are represented by an intermediate layer, and the onset of depression or of comorbid disease is represented by the output node. The occurrence of depression and the mechanism of the antidepressant action thus depend upon the weight of the interactions between the different end points, none of them being per se crucial to the onset of a depressive phenotype or to the antidepressant action. This model is heuristic to draw future lines of research concerning new antidepressant therapies, designing new animal models of depression and for a better understanding of the depressive pathology and of its comorbid pathology such as anxiety disorders. PMID:20132212

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: a longitudinal MRI study.

PubMed

Nicolo, John-Paul; Berger, Gregor E; Garner, Belinda A; Velakoulis, Dennis; Markulev, Connie; Kerr, Melissa; McGorry, Patrick D; Proffitt, Tina-Marie; McConchie, Mirabel; Pantelis, Christos; Wood, Stephen J

2010-01-01

Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic (r=-0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

PubMed

van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid hormone metabolism.

Growth, Hypothalamic Function, and Brain Ventricle Size in Mentally Retarded Subjects

ERIC Educational Resources Information Center

Leisti, S.; Iianainen, M.

1978-01-01

To determine whether moderate enlargement of the third brain ventricle or the temporal horns of the lateral ventricles was associated with hypothalamic dysfunction, 15 mentally retarded Ss (ages 12-25 years) with such characteristics were studies. (DLS)

Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress.

PubMed

Ghosal, Sriparna; Packard, Amy E B; Mahbod, Parinaz; McKlveen, Jessica M; Seeley, Randy J; Myers, Brent; Ulrich-Lai, Yvonne; Smith, Eric P; D'Alessio, David A; Herman, James P

2017-01-04

Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regional Glp1r knockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally, Glp1r knockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention. Dysfunctional stress responses are linked to a number of somatic and psychiatric diseases, emphasizing the importance of precise neuronal control of effector pathways. Pharmacological evidence suggests a role for glucagon-like peptide-1 (GLP-1) in modulating stress responses. Using a targeted knockdown of the GLP-1 receptor in the single-minded 1 neurons, we show dependence of paraventricular nucleus GLP-1 signaling in the coordination of neuroendocrine, autonomic, and behavioral responses to acute and chronic stress. To our knowledge, this is the first direct demonstration of an obligate brainstem-to-hypothalamus circuit orchestrating general stress excitation across multiple effector systems. These findings provide novel information regarding signaling pathways coordinating central control of whole-body stress reactivity. Copyright © 2017 the authors 0270-6474/17/370184-10$15.00/0.

Hypothalamic-pituitary cytokine network.

PubMed

Kariagina, Anastasia; Romanenko, Dmitry; Ren, Song-Guang; Chesnokova, Vera

2004-01-01

Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 microg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P<0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFalpha, IL-1beta, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.

Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome

PubMed Central

Lemche, Erwin; Chaban, Oleg S.; Lemche, Alexandra V.

2016-01-01

Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications. PMID:27147943

Cortisol Levels and Conduct Disorder in Adolescent Mothers

ERIC Educational Resources Information Center

Pajer, Kathleen; Gardner, William

2004-01-01

This study investigates the function of the hypothalamic-pituitary-adrenal (HPA) axis in adolescent antisocial girls. This question is important because disturbance of HPA functioning has been found in populations of violent adult males and antisocial adolescent males, suggesting that it may be a marker of a physiological disorder associated with…

Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

EPA Science Inventory

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

Prenatal Cocaine Exposure and Infant Cortisol Reactivity

ERIC Educational Resources Information Center

Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

2009-01-01

This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed,…

Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz

EPA Science Inventory

There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and ...

The Hypothalamic-Pituitary-Thyroid (HPT) Axis in Frogs and its Role in Frog Development and Reproduction

EPA Science Inventory

Metamorphosis of the amphibian tadpole is a thyroid hormone (TH)-dependent developmental process. For this reason, the tadpole is considered to be an ideal bioassay system to identify disruption of thyroid function by environmental contaminants. Here we provide an in-depth review...

78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... include the sex hormones (e.g., estrogen and androgen), the hypothalamic-pituitary-adrenal axis, the thyroid hormone, and the hormones involved in the feedback regulation of those components (e.g., gonadotropin releasing hormone and corticotropin). Changes in endocrine function can result in...

Crafting a gene expression timeline for the thyroid in the early-life stages of fathead minnows (Pimephales promelas)

EPA Science Inventory

The hypothalamic-pituitary-thyroid (HPT) axis plays a number of critical roles in chordate physiology including regulation of metabolism, growth, and development. While the role of the HPT axis and thyroid hormone signaling in mammalian and amphibian development is well establis...

Enhanced Cortisol Response to Stress in Children in Autism

ERIC Educational Resources Information Center

Spratt, Eve G.; Nicholas, Joyce S.; Brady, Kathleen T.; Carpenter, Laura A.; Hatcher, Charles R.; Meekins, Kirk A.; Furlanetto, Richard W.; Charles, Jane M.

2012-01-01

Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a…

Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

ERIC Educational Resources Information Center

Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

2012-01-01

Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

ERIC Educational Resources Information Center

Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

2012-01-01

Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

Breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure

USDA-ARS?s Scientific Manuscript database

Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it’s normally decreasing. To extend these fi...

Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

EPA Science Inventory

Antagonism of the androgen receptor (AR) is an environmentally-relevant mechanism through which the hypothalamic-pituitary-gonadal (HPG) axis of fish can be affected. However, there are few in vivo tests specific for the detection of chemicals that act as AR antagonists. In this ...

Identification of Androgen Receptor Antagonists in Fish Using a Simple Bioassay with the Fathead Minnow Pimephales promelas .

EPA Science Inventory

Considerable effort has been expended on the development of bioassays to detect chemicals that affect endocrine function controlled by the vertebrate hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). Antagonism of the androgen receptor (AR)...

Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: Computational Modeling

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC)...

Bittersweet: Real-Time, Dynamic Changes in Blood Glucose Levels during an Acute Ozone Exposure in Rats

EPA Science Inventory

In humans and rats, acute exposures to ozone have been shown to activate the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes to induce multi-organ metabolic alterations including impaired glucose homeostasis. These findings have largely been gleaned from on...

Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

USDA-ARS?s Scientific Manuscript database

Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

POTENTIAL ROLE OF TUBERO-INFUNDIBULAR DOPAMINERGIC NEURONS IN THE DISRUPTION OF PITUITARY HORMONE SECRETION BY ATRAZINE

EPA Science Inventory

Previously, we demonstrated that atrazine suppressed the ovulatory surge of luteininzing hormone and disrupted estrous cycles in the female rat. We also reported that this disruption of ovulation is likely the result of atrazine's effect on hypothalamic gonadotropin hormone rele...

Dynamic Nature of Alterations in the Endocrine System of Fathead Minnows Exposed to the Fungicide Prochloraz, Presentation

EPA Science Inventory

The vertebrate hypothalamic-pituitary-gonadal (HPG) axis is controlled through various feedback mechanisms that ideally serve to maintain a dynamic homeostasis of the system in the face of changing environmental conditions, including exposure to chemical stressors. In these stud...

Development of Thyroid Gland Specific Markers of Hypothalamic-pituitary-thyroid Axis Disruption in the Amphibian Model Species Xenopus laevis

EPA Science Inventory

The focus of the research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis.

Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

EPA Science Inventory

Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. The presen...

Effects of Fadrozole, Ketoconazole, and 17β-trenbolone on Ex Vivo Steroidogenesis in the Fathead Minnow

EPA Science Inventory

A variety of endocrine-disrupting chemicals have the ability to disrupt steroidogenesis through interaction with the hypothalamic-pituitary-gonadal (HPG) axis. We examined the effects of the competitive aromatase inhibitor fadrozole (0, 3, and 30 g/L), the cytochrome P450 enzyme...

EDC testing in the future: Exploring roles of pathway-based in silico, in vitro and in vivo methods

EPA Science Inventory

Many thoroughly validated, robust tests with both mammalian and non-mammalian models have been developed to identify chemicals with the potential to impact endocrine pathways associated with the hypothalamic-pituitary-gonadal (HPG) and thyroidal axes. In the US, for example, the...

HPLC-ICP/MS Analysis of Thyroid Hormone and Related Iodinated Compounds in Tissues and Media

EPA Science Inventory

Quantifying thyroid hormone (TH) and the synthetic precursors and metabolic products of TH is important for developing models of the hypothalamic-pituitary-thyroid (HPT) axis as well as for understanding the effects of xenobiotics on HPT axis function. In this study, the developm...

A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency

EPA Science Inventory

A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quanti...

Salivary Cortisol Profiles of Children with Hearing Loss

ERIC Educational Resources Information Center

Bess, Fred H.; Gustafson, Samantha J.; Corbett, Blythe A.; Lambert, E. Warren; Camarata, Stephen M.; Hornsby, Benjamin W. Y.

2016-01-01

Objectives: It has long been speculated that effortful listening places children with hearing loss at risk for fatigue. School-age children with hearing loss experiencing cumulative stress and listening fatigue on a daily basis might undergo dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in elevated or flattened…

Genetic disorders of the anterior pituitary gland.

PubMed

Teller, W M

1985-01-01

This survey deals with disorders caused by genetically disturbed function of the anterior pituitary gland. Genetic Dwarfism may be caused by isolated growth hormone deficiency (IGHD) or panpituitary diseases, such as congenital absence of the pituitary or familial panhypopituitarism. Genetic disturbances of isolated pituitary hormone secretion without dwarfism may occur as isolated gonadotropin deficiency (IGD), isolated luteinizing hormone deficiency ("fertile eunuch"), Kallmann syndrome (olfactogenital dysplasia), isolated thyrotropin deficiency (ITD) and isolated corticotropin deficiency (ICD). Pituitary dysfunction may also be associated with other genetic disease entities.

Altered Regulation of Gene and Protein Expression of Hypothalamic-Pituitary-Adrenal Axis Components in an Immature Rat Model of Chronic Stress

PubMed Central

Avishai-Eliner, S.; Gilles, E. E.; Eghbal-Ahmadi, M.; Bar-El, Y.; Baram, T. Z.

2011-01-01

Chronic stress early in postnatal life influences hormonal and behavioural responses to stress persistently, but the mechanisms and molecular cascades that are involved in this process have not been clarified. To approach these issues, a chronic stress paradigm for the neonatal rat, using limited bedding material to alter the cage environment, was devised. In 9-day-old rats subjected to this chronic stress for 1 week, significant and striking changes in the expression and release patterns of key molecules that govern the neuroendocrine stress responses were observed. The presence of sustained stress was evident from enhanced activation of peripheral elements of the neuroendocrine stress response, i.e. increased basal plasma corticosterone concentrations, high adrenal weight and decreased body weight. Central regulatory elements of the neuroendocrine stress response were perturbed, including reduced expression of hypothalamic corticotropin-releasing hormone that, surprisingly, was accompanied by reduced glucocorticoid receptor expression. Thus, the effects of chronic sustained stress in the neonatal rat on the hypothalamic-pituitary-adrenal axis included substantial changes in the expression and activity of major regulators of this axis. Importantly, the changes induced by this chronic stress differed substantially from those related to acute or recurrent stress, providing a novel model for studying the long-term effects of chronic, early life stress on neuroendocrine functions throughout life. PMID:11578530

Loss of Gq/11 Family G Proteins in the Nervous System Causes Pituitary Somatotroph Hypoplasia and Dwarfism in Mice

PubMed Central

Wettschureck, N.; Moers, A.; Wallenwein, B.; Parlow, A. F.; Maser-Gluth, C.; Offermanns, S.

2005-01-01

Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter and hormone receptors and have therefore been implicated in various functions of the nervous system. Using the Cre/loxP system, we generated mice which lack the genes coding for the α subunits of the two main members of the Gq/11 family, gnaq and gna11, selectively in neuronal and glial precursor cells. Mice with defective gnaq and gna11 genes were morphologically normal, but they died shortly after birth. Mice carrying a single gna11 allele survived the early postnatal period but died within 3 to 6 weeks as anorectic dwarfs. In these mice, postnatal proliferation of pituitary somatotroph cells was strongly impaired, and plasma growth hormone (GH) levels were reduced to 15%. Hypothalamic levels of GH-releasing hormone (GHRH), an important stimulator of somatotroph proliferation, were strongly decreased, and exogenous administration of GHRH restored normal proliferation. The hypothalamic effects of ghrelin, a regulator of GHRH production and food intake, were reduced in these mice, suggesting that an impairment of ghrelin receptor signaling might contribute to GHRH deficiency and abnormal eating behavior. Taken together, our findings show that Gq/11 signaling is required for normal hypothalamic function and that impairment of this signaling pathway causes somatotroph hypoplasia, dwarfism, and anorexia. PMID:15713647

Role of the endocannabinoid system in the neuroendocrine responses to inflammation.

PubMed

De Laurentiis, Andrea; Araujo, Hugo A; Rettori, Valeria

2014-01-01

A few years ago the endocannabinoid system has been recognized as a major neuromodulatory system whose main functions are to exert and maintain the body homeostasis. Several different endocannabinoids are synthesized in a broad class of cell types, including those in the brain and the immune system; they bind to cannabinoid G-protein-coupled receptors, having profound effects on a variety of behavioral, neuroendocrine and autonomic functions. The coordinated neural, immune, behavioral and endocrine responses to inflammation are orchestrated to provide an important defense against infections and help homeostasis restoration in the body. These responses are executed and controlled mainly by the hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal system is essential for survival and plays a role recovering the homeostasis under a variety of stress conditions, including inflammation and infection. Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions. In the present review we focused on the endocannabinoids actions on the neuroendocrine response to inflammation and infection. We provide a detailed overview of the current understanding of the role of the endocannabinoid system in the recovering of homeostasis as well as potential pharmacological therapies based on the manipulation of endocannabinoid system components that could provide novel treatments for a wide range of disorders.

Variations of rat thyroid activity during exposure to high environmental temperature (34 degrees C). Relation between hypothalamic pituitary and thyroid hormone levels.

PubMed

Rousset, B; Cure, M

1975-01-01

Changes in thyroid activity and variations in the hypthalamo-pituitary-thyroid hormone levels were examined in rats exposed to heat (34 degrees C)for3 weeks. Thyroid activity evaluated histologically (epithelium/colloid ratio, nuclear size) by radioiodine exploration (24 hrs 125 I uptake, ratio of mono- to di-125 iodotyrosines - MIT/DIT, ratio of tri- to tetra-125 iodothyronines-T3/T4, and plasma 125I-T4 and assay of plasma T4, evolves in a triphasic manner. 1.a depression phase between day 0 and day 2.5. 2. a rebound of thyroid activity between day 2.5 and day 9.3 a stabilization of thyroid parameters from day 9 to day 24. These results indicate adaptation of thyroid function to heat after 3 weeks. In phase i, plasma TSH )MeKenzie bioassay) fell to undectable levels concurrent with a 50% decrease in hypothalamic TRH (in vitro assay). Plasma TSH peaked on day 4.5, fell on day 9.5 and returned progressively to initial levels. Hypothalamic TRH returned to initial levels after 6.5 days. The rapid and simultaneous decrease in hypothalamic TRH, plasma TSH, plasma T4 and thyroid activity by the 36th hour of heat exposure (34 degrees C) suggests initiation at the hypothalamic level. In the secound phase, the rebound in thyroid activity is presumably due to the peak in circulating TSH in ralation to the marked decrease in plasma T4. The oscillations of phase 2 and the stabilization of all the thyroid parameters in phase 3 may be the reflection of an apparent discrepancy remains between a low plasma T4 and a normal or subnormal plasma TSH. A modification in the "set point" for the control of TSH secretion is discussed.

The Hypothalamic-Pituitary-Adrenal Axis and Serotonin Metabolism in Individual Brain Nuclei of Mice with Genetic Disruption of the NK1 Receptor Exposed to Acute Stress.

PubMed

Culman, Juraj; Mühlenhoff, Stephan; Blume, Annegret; Hedderich, Jürgen; Lützen, Ulf; Hunt, Stephen P; Rupniak, Nadia M J; Zhao, Yi

2018-06-15

Mice lacking the substance P (SP) neurokinin-1 (NK1) receptor (NK1R-/-mice) were used to investigate whether SP affects serotonin (5-HT) function in the brain and to assess the effects of acute immobilisation stress on the hypothalamic-pituitary-adrenocortical (HPA) axis and 5-HT turnover in individual brain nuclei. Basal HPA activity and the expression of hypothalamic corticotropin-releasing hormone (CRH) in wild-type (WT)- and NK1R-/- mice were identical. Stress-induced increases in plasma ACTH concentration were considerably higher in NK1R-/- mice than in WT mice while corticosterone concentrations were equally elevated in both mouse lines. Acute stress did not alter the expression of CRH. In the dorsal raphe nucleus (DRN), basal 5-HT turnover was increased in NK1R-/- mice and a 15 min stress further magnified 5-HT utilisation in this region. In the frontoparietal cortex, medial prefrontal cortex, central nucleus of amygdala, and the hippocampal CA1 region, stress increased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) concentrations to a similar extent in WT and NK1R-/- mice. 5-HT turnover in the hypothalamic paraventricular nucleus was not affected by stress, but stress induced similar increases in 5-HT and 5-HIAA in the ventromedial and dorsomedial hypothalamic nuclei in WT and NK1R-/- mice. Our findings indicate that NK1 receptor activation suppresses ACTH release during acute stress but does not exert sustained inhibition of the HPA axis. Genetic deletion of the NK1 receptor accelerates 5-HT turnover in DRN under basal and stress conditions. No differences between the responses of serotonergic system to acute stress in WT and NK1R-/- mice occur in forebrain nuclei linked to the regulation of anxiety and neuroendocrine stress responses.

Norman M. Dott, master of hypothalamic craniopharyngioma surgery: the decisive mentoring of Harvey Cushing and Percival Bailey at Peter Bent Brigham Hospital.

PubMed

Prieto, Ruth; Pascual, José M

2017-10-01

Norman McOmish Dott (1897-1973) developed surgical neurology in Edinburgh, Scotland, and was a scholar of worldwide renown. One of Dott's most notable contributions to neurosurgery was his understanding of hypothalamic physiology, mostly acquired through the comprehensive study of patients with lesions involving this region of the diencephalon, particularly craniopharyngiomas (CPs). Recognition of symptoms caused by hypothalamic disturbances allowed him to predict the accurate anatomical relationships between CPs and the hypothalamus, despite the rudimentary radiological methods available during the 1930s. His sophisticated knowledge permitted Dott to perform radical removals of CPs originating within the third ventricle floor with acceptable success. Between 1934 and 1937, he operated on 4 CP cases originating in the hypothalamus, achieving a satisfactory postoperative outcome in 3 of the 4 patients. Aware of the strong attachment of hypothalamic CPs to the infundibulo-tuberal area, Dott used a double transbasal and transventricular approach to these lesions, a strategy providing an optimal view and control of the tumor boundaries. The decisive mentorship of several legendary figures of physiology and neurosurgery greatly influenced Dott's surgical evolution. The experimental pituitary gland work he performed with Sir Edward Sharpey-Schäfer at the beginning of his career stirred Dott's curiosity about the issue of hypothalamus-pituitary relationships. As a result, he decided to move to Peter Bent Brigham Hospital (Boston, Massachusetts) in 1923, to train in neurosurgery and neuropathology under the guidance of the leaders in these fields, Harvey Williams Cushing (1869-1939) and Percival Sylvester Bailey (1892-1973). They inspired the young Dott and shared with him their clinical and pathological expertise, in addition to their surgical strategies for best approaching and removing these challenging tumors. In time, Dott would come to surpass his mentors. This paper aims to credit Norman M. Dott for his decisive, modern contributions to hypothalamic CP surgery.

Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group.

PubMed

Secombe, C J; Bailey, S R; de Laat, M A; Hughes, K J; Stewart, A S; Sonis, J M; Tan, Rhh

2018-06-03

The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder. © 2018 Australian Veterinary Association.

The thyroid axis in ageing.

PubMed

Leitol, Holger; Behrends, Jens; Brabant, Georg

2002-01-01

The hypothalmo-pituitary thyroid axis, among various endocrine systems, undergoes physiological alterations associated with the ageing process. Directly age-related changes have to be distinguished from indirect modifications which are caused by simultaneous thyroidal or non-thyroidal illness or other physiological or pathophysiological states whose incidence increases with age. In summary, direct changes of the hypothalmo-pituitary-thyroid axis seem to be subtle and suggestive of a decreased hypothalamic stimulation of thyroid function. In parallel, disease-specific alterations such as the development of thyroid autonomy or changes in energy intake or sleep lead to pronounced alterations of thyroid function with age which may dominate the underlying ageing of the hypothalmo-pituitary thyroid axis itself. The following article attempts to delineate some aspects of the interplay of the regulation of thyroid function and the ageing process.

The hypothalamic neuropeptide oxytocin is required for formation of the neurovascular interface of the pituitary.

PubMed

Gutnick, Amos; Blechman, Janna; Kaslin, Jan; Herwig, Lukas; Belting, Heinz-Georg; Affolter, Markus; Bonkowsky, Joshua L; Levkowitz, Gil

2011-10-18

The hypothalamo-neurohypophyseal system (HNS) is the neurovascular structure through which the hypothalamic neuropeptides oxytocin and arginine-vasopressin exit the brain into the bloodstream, where they go on to affect peripheral physiology. Here, we investigate the molecular cues that regulate the neurovascular contact between hypothalamic axons and neurohypophyseal capillaries of the zebrafish. We developed a transgenic system in which both hypothalamic axons and neurohypophyseal vasculature can be analyzed in vivo. We identified the cellular organization of the zebrafish HNS as well as the dynamic processes that contribute to formation of the HNS neurovascular interface. We show that formation of this interface is regulated during development by local release of oxytocin, which affects endothelial morphogenesis. This cell communication process is essential for the establishment of a tight axovasal interface between the neurons and blood vessels of the HNS. We present a unique example of axons affecting endothelial morphogenesis through secretion of a neuropeptide. Copyright © 2011 Elsevier Inc. All rights reserved.

Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine α-Amidating Monooxygenase by Dietary Copper

PubMed Central

Bousquet-Moore, D.; Ma, X. M.; Nillni, E. A.; Czyzyk, T. A.; Pintar, J. E.; Eipper, B. A.; Mains, R. E.

2009-01-01

Amidated peptides are critically involved in many physiological functions. Genetic deletion of peptidylglycine α-amidating monooxygenase (PAM), the only enzyme that can synthesize these peptides, is embryonically lethal. The goal of the present study was the identification of physiological functions impaired by haploinsufficiency of PAM. Regulation of the hypothalamic-pituitary-thyroid axis and body temperature, functions requiring contributions from multiple amidated peptides, were selected for evaluation. Based on serum T4 and pituitary TSH-β mRNA levels, mice heterozygous for PAM (PAM+/−) were euthyroid at baseline. Feedback within the hypothalamic-pituitary-thyroid axis was impaired in PAM+/− mice made hypothyroid using a low iodine/propylthiouracil diet. Despite their normal endocrine response to cold, PAM+/− mice were unable to maintain body temperature as well as wild-type littermates when kept in a 4 C environment. When provided with additional dietary copper, PAM+/− mice maintained body temperature as well as wild-type mice. Pharmacological activation of vasoconstriction or shivering also allowed PAM+/− mice to maintain body temperature. Cold-induced vasoconstriction was deficient in PAM+/− mice. This deficit was eliminated in PAM+/− mice receiving a diet with supplemental copper. These results suggest that dietary deficiency of copper, coupled with genetic deficits in PAM, could result in physiological deficits in humans. PMID:19022883

Outcome of diabetes insipidus in patients with Rathke's cleft cysts.

PubMed

Oishi, Masahiro; Hayashi, Yasuhiko; Sasagawa, Yasuo; Kita, Daisuke; Tachibana, Osamu; Nakada, Mitsutoshi

2018-04-01

It is well-known that Rathke's cleft cysts (RCCs) infrequently cause headache, endocrinological dysfunction, and visual disturbance, and in rare cases, cause diabetes insipidus (DI). Although surgical evacuation of the cyst content can result in high rates of symptomatic improvement, not only the treatment efficacy but also the pathophysiology of DI with RCC are undetermined. The aim of this study is to elucidate the underlying mechanisms and outcomes of DI associated with RCCs. We retrospectively studied 109 patients with RCCs treated at Kanazawa University Hospital between 2000 and 2016. Their age, sex, symptoms, endocrinological status, DI, visual disturbance, neuroradiological findings, pathological appearances, and pre-/post-operative hormone levels and status of anti-diuretic hormone replacements were assessed. Among 109 cases of RCCs, five cases (4.6%, 2 males and 3 females) manifested with DI as initial presentation were included. These five cases could be divided into two types: the acute type and the chronic type, based on the onset and duration of symptoms. Three acute onset cases presented with not only strong thirst but also sudden headaches without pituitary dysfunction, whereas the two chronic onset cases presented with chronic headaches and hypopituitarism. Pathological examination in the acute type revealed inflammatory cell infiltration into only the posterior lobe of the pituitary and disruption of the cyst wall adjacent to the posterior lobe, which might suggest RCC rupture. In contrast, the chronic type showed inflammatory cell infiltration into both the anterior and posterior lobes of the pituitary and thickened fibrosis beneath the cyst wall. Postoperatively, two cases of the acute type could be controlled with a smaller amount of 1-deamino-8-D-arginine vasopressin (DDAVP) than that required preoperatively, whereas no change was observed in the cases of the chronic type. The cases of DI onset caused by RCCs could be divided into the acute type and the chronic type. In the chronic type, surgical treatment could not affect the status of DI. However, in acute type, urgent surgical intervention partially relieved DI. Copyright © 2018 Elsevier B.V. All rights reserved.

Transcranial Evacuation of Atypical Progressive Supradiaphragmatic Hematoma After Transsphenoidal Complete Resection of Pituitary Adenoma.

PubMed

Metwali, Hussam; Fahlbusch, Rudolf

2017-06-01

Supradiaphragmatic hematoma is a type of hematoma that occurs after transsphenoidal (TS) resection of pituitary adenoma and requires special management. Two patients had symptomatic supradiaphragmatic hematomas after total TS resection of pituitary adenomas in the absence of vascular anomalies. Both patients also had hydrocephalus at the time of diagnosis of the hematoma. The initial endoscopic endonasal inspection showed no subdiaphragmatic bleeding. The hematoma was evacuated via a frontolateral approach after insertion of an external ventricular drain (EVD). The supradiaphragmatic hematoma could be clinically and radiologically distinguished. It presented early with visual deterioration without headache. The patients developed hydrocephalus, which was associated with deterioration of level of consciousness. Radiologically, the hematoma filled the suprasellar space and was associated with the extension of bleeding in the basal cisterns. Recovery was good in both patients. There were no permanent neurologic deficits. The EVD was removed in both patients. One patient required a ventriculoperitoneal shunt because of delayed hydrocephalus. Supradiaphragmatic hematoma can be clinically and radiologically distinguished from other types of hematoma occurring after TS resection of pituitary adenoma. Transcranial surgery should be performed to manage supradiaphragmatic hematoma, when symptomatic. Insertion of an EVD at the time of evacuation is mandatory to relax the brain and to alleviate the hydrocephalus. Copyright © 2017 Elsevier Inc. All rights reserved.

Pituitary adenylate cyclase-activating polypeptide stimulates glucose production via the hepatic sympathetic innervation in rats.

PubMed

Yi, Chun-Xia; Sun, Ning; Ackermans, Mariette T; Alkemade, Anneke; Foppen, Ewout; Shi, Jing; Serlie, Mireille J; Buijs, Ruud M; Fliers, Eric; Kalsbeek, Andries

2010-07-01

The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. Intracerebroventricular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production.

Glutaminyl Cyclase Knock-out Mice Exhibit Slight Hypothyroidism but No Hypogonadism

PubMed Central

Schilling, Stephan; Kohlmann, Stephanie; Bäuscher, Christoph; Sedlmeier, Reinhard; Koch, Birgit; Eichentopf, Rico; Becker, Andreas; Cynis, Holger; Hoffmann, Torsten; Berg, Sabine; Freyse, Ernst-Joachim; von Hörsten, Stephan; Rossner, Steffen; Graubner, Sigrid; Demuth, Hans-Ulrich

2011-01-01

Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate (pGlu) residues at the N terminus of peptides and proteins. Hypothalamic pGlu hormones, such as thyrotropin-releasing hormone and gonadotropin-releasing hormone are essential for regulation of metabolism and fertility in the hypothalamic pituitary thyroid and gonadal axes, respectively. Here, we analyzed the consequences of constitutive genetic QC ablation on endocrine functions and on the behavior of adult mice. Adult homozygous QC knock-out mice are fertile and behave indistinguishably from wild type mice in tests of motor function, cognition, general activity, and ingestion behavior. The QC knock-out results in a dramatic drop of enzyme activity in the brain, especially in hypothalamus and in plasma. Other peripheral organs like liver and spleen still contain QC activity, which is most likely caused by its homolog isoQC. The serum gonadotropin-releasing hormone, TSH, and testosterone concentrations were not changed by QC depletion. The serum thyroxine was decreased by 24% in homozygous QC knock-out animals, suggesting a mild hypothyroidism. QC knock-out mice were indistinguishable from wild type with regard to blood glucose and glucose tolerance, thus differing from reports of thyrotropin-releasing hormone knock-out mice significantly. The results suggest a significant formation of the hypothalamic pGlu hormones by alternative mechanisms, like spontaneous cyclization or conversion by isoQC. The different effects of QC depletion on the hypothalamic pituitary thyroid and gonadal axes might indicate slightly different modes of substrate conversion of both enzymes. The absence of significant abnormalities in QC knock-out mice suggests the presence of a therapeutic window for suppression of QC activity in current drug development. PMID:21330373

Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas.

PubMed

Barbieri, Federica; Bajetto, Adriana; Stumm, Ralf; Pattarozzi, Alessandra; Porcile, Carola; Zona, Gianluigi; Dorcaratto, Alessandra; Ravetti, Jean-Louis; Minuto, Francesco; Spaziante, Renato; Schettini, Gennaro; Ferone, Diego; Florio, Tullio

2008-08-15

Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone-secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development in humans.

Cocaine-and Amphetamine Regulated Transcript (CART) Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland

PubMed Central

Mortensen, Amanda H.

2016-01-01

Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1. PMID:27685990

Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation.

PubMed

Paterniti, Irene; Cordaro, Marika; Navarra, Michele; Esposito, Emanuela; Cuzzocrea, Salvatore

2015-01-01

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.

Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain injury

PubMed Central

Hari Kumar, K. V. S.; Swamy, M. N.; Khan, M. A.

2016-01-01

Background: Traumatic brain injury (TBI) is common in young soldiers of armed forces leading to significant morbidity and mortality. We studied the prevalence of hypopituitarism following TBI and its association with trauma severity. Materials and Methods: We conducted a 12-month prospective study of 56 TBI patients for the presence of hormonal dysfunction. Hormonal parameters were estimated during the early phase (0–10 days posttraumatically) and after 6 and 12 months. Dynamic testing was done when required, and the results were analyzed by appropriate statistical methods. Results: Hormonal dysfunction was seen in 39 of the 56 (70%) patients at initial assessment. Persisting pituitary deficiencies are seen in 7 and 8 patients at the end of 6 months and 12 months, respectively. Hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency are the most common diagnoses. Initial severe TBI and plurihormonal involvement predicted the long-term hypopituitarism. Conclusion: Early hypopituitarism was common in severe TBI, but recovers in majority. Evaluation for the occult pituitary dysfunction is required during the rehabilitation of TBI patients. PMID:27867878

Dietary Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

PubMed Central

Lema, Sean C.; Dickey, Jon T.; Schultz, Irvin R.; Swanson, Penny

2008-01-01

Background Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues. Objective We examined the effects of dietary exposure to 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47)—commonly the highest concentrated PBDE in human tissues—on plasma TH levels and on gene transcripts for glycoprotein hormone α-subunit (GPHα) and thyrotropin β-subunit (TSHβ) in the pituitary gland, the autoinduced TH receptors α and β in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain. Methods Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 μg/pair/day or 12.3 μg/pair/day) for 21 days. Results Minnows exposed to PBDE-47 had depressed plasma thyroxine (T4), but not 3,5,3′-triiodothyronine (T3). This decline in T4 was accompanied by elevated mRNA levels for TStHβ (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor αin the brain of females and decreased mRNA for TH receptor β in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB. Conclusions Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants. PMID:19079722

Pineal-mediated inhibition of prolactin cell activity: Investigation of dopaminergic involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burns, D.M.

The present studies in the male Syrian hamster addressed two issues. First, it was of interest to determine if anterior pituitaries of long photoperiod-exposed male hamsters possess dopamine receptors, which are presumably necessary for responsiveness to dopamine. This was accomplished by analysis of {sup 3}H-spiperone binding to anterior pituitary membranes. Second, possible changes in pituitary sensitivity to dopamine were assessed by comparison of dose response curves for the inhibition by dopamine of prolactin release from hemipituitaries incubated in vitro from both long and short photoperiod-exposed animals over a series of time points from three to fifteen weeks. In the secondmore » series of experiments, adult female F344 rats received daily injection of melatonin or saline vehicle. After two weeks, half of the animals were sacrificed for analysis of {sup 3}H-spiperone binding to anterior pituitary membranes, measurement of hypothalamic dopamine turnover and analysis of in vitro pituitary sensitivity to dopamine. The remaining animals received subcutaneous implants containing DES and injections were continued on the same schedule until sacrifice four weeks later for measurement of the same parameters.« less

Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos-Danellis, J.

1979-01-01

Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0-5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.

Direct stimulation of pituitary prolactin release by glutamate.

PubMed

Login, I S

1990-01-01

The ability of glutamate and other excitatory amino acids to stimulate prolactin secretion when administered to adult animals is hypothesized to depend on a central site of action in the brain, but there are no data to support this position. An alternative hypothesis was tested that glutamate would stimulate prolactin release when applied directly to primary cultures of dispersed adult female rat anterior pituitary cells studied in a perifusion protocol. Glutamate increased the rate of prolactin release within two minutes in a self-limited manner. Glutamate-stimulated prolactin release was augmented about 4-fold by elimination of magnesium from the perfusate and was associated with stimulation of pituitary calcium flux. Ketamine and MK-801 both reduced the basal rate of prolactin release and abolished the effects of glutamate. Pituitary cells of 10-day-old rats responded similarly to glutamate. Exposure to glutamate did not influence subsequent responses to physiological hypothalamic secretagogues, thus the likelihood of toxicity was minimized. These results suggest that the N-methyl-D-aspartate (NMDA) subclass of the glutamate receptor complex is involved. Prolactin secretion may be regulated physiologically through a functional glutamate receptor on pituitary cells.

Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence.

PubMed

Deligeoroglou, E K; Creatsas, G K

2015-08-01

Excessive uterine bleeding during the early years after menarche can be worrisome to the girl and her parents. The most prevalent diagnosis set is Dysfunctional uterine bleeding (DUB), after thorough examination and exclusion of other causes of abnormal uterine bleeding. The aim of this article was to review our knowledge and share our experience as tertiary reference center of pediatric-adolescent gynecology in Greece. We conducted a review of current literature using Pubmed and MedLine as our primary databases, as well as providing commentary considering work up, treatment and follow-up of our DUB patients. Insufficient progesterone production and subsequent abnormal shedding of the endometrium appears to orchestrate the pathophysiology of DUB in adolescence. Hypothalamic-pituitary-ovarian (HPO) axis immaturity right after menarche, is usually the most plausible cause. Nevertheless, it is necessary to exclude other, possibly even life-threatening causes. Complete work up including physical examination, laboratory and imaging studies (complete blood count, b-HCG, hormonal levels and ultrasonography) is needed, and appropriate treatment with combined oral contraceptives is administered accordingly. Although menstrual disorders are very common in early adolescence, a severe episode of DUB should always be thoroughly attended by any physician. Follow-up should be offered in all young patients due to high incidence of recurrence or subsequent development of endocrine disorders such as Polycystic Ovary Syndrome (PCOS).

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

PubMed

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Prenatal Stress and Risk for Psychopathology: Specific Effects or Induction of General Susceptibility?

ERIC Educational Resources Information Center

Huizink, Anja C.; Mulder, Edu J. H.; Buitelaar, Jan K.

2004-01-01

This review focuses on prenatal stress as a risk factor for psychopathology. Evidence from animal studies is summarized, and the relevance of prenatal stress models in animals for human studies is discussed. In the offspring of prenatally stressed animals, overactivity and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal…

Sex Differences in Salivary Cortisol, Alpha-Amylase, and Psychological Functioning Following Hurricane Katrina

ERIC Educational Resources Information Center

Vigil, Jacob M.; Geary, David C.; Granger, Douglas A.; Flinn, Mark V.

2010-01-01

The study examines group and individual differences in psychological functioning and hypothalamic-pituitary-adrenal and sympathetic nervous system (SNS) activity among adolescents displaced by Hurricane Katrina and living in a U.S. government relocation camp (n = 62, ages 12-19 years) 2 months postdisaster. Levels of salivary cortisol, salivary…

Effortful Control and Parenting: Associations with HPA Axis Reactivity in Early Childhood

ERIC Educational Resources Information Center

Kryski, Katie R.; Dougherty, Lea R.; Dyson, Margaret W.; Olino, Thomas M.; Laptook, Rebecca S.; Klein, Daniel N.; Hayden, Elizabeth P.

2013-01-01

While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however,…

Investigations of HPA Function and the Enduring Consequences of Stressors in Adolescence in Animal Models

ERIC Educational Resources Information Center

McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, Catherine; Waters, Patti

2010-01-01

Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system.…

A computational model linking oocyte growth and spawning to the hypothalamic-pituitary-gonadal axis in fathead minnow (Pimephales promelas)

EPA Science Inventory

Reproduction is vital to the survival of all living organisms, and reproductive toxicity is an important outcome in determining the ecological risks of chemicals in the environment. To evaluate reproductive toxicity, fathead minnow fecundity, as measured by the average number of...

Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

ERIC Educational Resources Information Center

Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

2010-01-01

Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

Classroom Emotional Support Predicts Differences in Preschool Children's Cortisol and Alpha-Amylase Levels

ERIC Educational Resources Information Center

Hatfield, Bridget E.; Hestenes, Linda L.; Kintner-Duffy, Victoria L.; O'Brien, Marion

2013-01-01

Accumulating evidence suggests children enrolled in full-time child care often display afternoon elevations of the hormone cortisol, which is an indicator of stress. Recent advances in immunoassays allow for measurement of activity in the hypothalamic-pituitary-adrenal axis and the autonomic sympathetic nervous system from saliva, and measurement…

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

EPA Science Inventory

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

Salivary Cortisol as a Predictor of Socioemotional Adjustment during Kindergarten: A Prospective Study.

ERIC Educational Resources Information Center

Smider, N. A.; Essex, M. J.; Kalin, N. H.; Buss, K. A.; Klein, M. H.; Davidson, R. J.; Goldsmith, H. H.

2002-01-01

Examined whether activation of the hypothalamic-pituitary-adrenocortical system, as indexed by average home afternoon levels of cortisol in children age 4.5 years, would predict socioemotional adjustment measured a year and a half later. Found that higher cortisol levels were associated with withdrawal-type behaviors of internalizing and social…

The rodent estrous cycle: Characterization of vaginal cytology and its utility in toxicological studies

EPA Science Inventory

An evaluation of the estrous cycle in laboratory rodents can be a useful measure of the integrity of the hypothalamic-pituitary-ovarian reproductive axis. It can also serve as a way of insuring that animals exhibiting abnormal cycling patterns are disincluded from a study prior t...

75 FR 10255 - FIFRA Scientific Advisory Panel; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... this meeting is a discretionary function of the Agency. The selection of scientists to serve on FIFRA SAP is based on the function of the panel and the expertise needed to address the Agency's charge to... on the hypothalamic-pituitary-adrenal (HPA) axis, immune system, prostate, brain, and the enzyme...

Effects of a Short-term Exposure to the Fungicide Prochloraz on Endocrine Function and Gene Expression in Female Fathead Minnows (Pimephales promelas)

EPA Science Inventory

Prochloraz is a fungicide known to cause endocrine disruption through effects on the hypothalamic-pituitary-gonadal (HPG) axis. To determine the short-term impacts of prochloraz on gene expression and steroid production, adult female fathead minnows (Pimephales promelas) were exp...

AVPR1A alleles are pleiotropic sources of variation in age at puberty and reproductive longevity in sows

USDA-ARS?s Scientific Manuscript database

Age at puberty is a moderately heritable trait and an early indicator of sow reproductive longevity. Gilts that express first estrus early in life are characterized by improved reproductive longevity and lifetime productivity. These traits are dependent on the function of the hypothalamic-pituitary-...

Infant cortisol concentrations do not differ by group in a randomized controlled trial of lipid based nutrient supplements among mothers and infants in Malawi

USDA-ARS?s Scientific Manuscript database

Background: Prenatal malnutrition and stress have been associated with the regulation of the offspring hypothalamic-pituitary-adrenal (HPA) axis. Objective: To evaluate whether maternal and infant nutritional supplementation was associated with salivary cortisol concentrations in Malawian infants. ...

Stress, Cortisol, and Externalizing Behavior in Adolescent Males: An Examination in the Context of Multisystemic Therapy

ERIC Educational Resources Information Center

Schechter, Julia C.; Brennan, Patricia A.; Cunningham, Phillippe B.; Foster, Sharon L.; Whitmore, Elizabeth

2012-01-01

Stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation have been associated with externalizing behavior in adolescence, but few studies have examined these factors in a treatment context. This study investigated the relationship between stress, cortisol, and externalizing behavior among 120 adolescent males (mean age = 15) receiving…

Ghrelin stimulates growth hormone release from the pituitary via hypothalamic growth hormone-releasing hormone neurons in the cichlid, Oreochromis niloticus

USDA-ARS?s Scientific Manuscript database

Ghrelin, a gastric peptide, is implicated in a multiplicity of biological functions, including energy homeostasis and reproduction. Neuronal systems that are involved in energy homeostasis as well as reproduction traverse the hypothalamus, however, the mechanism by which they control energy homeosta...

Gene transcription ontogeny of hypothalamic-pituitary-thyroid-axis development in early-life stage fathead minnow and zebrafish

EPA Science Inventory

Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in develo...

A SYSTEMS APPROACH TO CHARACTERIZING AND PREDICTING THYROID TOXICITY USING AN AMPHIBIAN MODEL

EPA Science Inventory

The EPA was recently mandated to evaluate the potential effects of chemicals on endocrine function and has identified Xenopus as a model organism to use as the basis for a thyroid disruption screening assay. The main objective of this work is to develop a hypothalamic-pituitary-t...

In Search of HPA Axis Dysregulation in Child and Adolescent Depression

ERIC Educational Resources Information Center

Guerry, John D.; Hastings, Paul D.

2011-01-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

Social Behavior and Cortisol Reactivity in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Hessl, David; Glaser, Bronwyn; Dyer-Friedman, Jennifer; Reiss, Allan L.

2006-01-01

Objective: To examine the association between limbic-hypothalamic-pituitary-adrenal (L-HPA) axis reactivity and social behavior in children with fragile X syndrome (FXS). Method: Salivary cortisol changes and concurrent anxiety-related behaviors consistent with the behavioral phenotype of FXS were measured in 90 children with the fragile X full…

Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

EPA Science Inventory

A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

Environmental exposure and altered menstrual function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keye, W.R. Jr.

The impact of environmental agents and occupational factors on hypothalamic and pituitary function and menstruation are poorly understood. To date, most research related to environment, occupation, and reproduction has focused on pregnancy outcome, not menstrual function. It is imperative, however, that menstrual function be considered as an outcome variable in the study of reproduction and occupation.

Developing predictive approaches to characterize adaptive responses of the reproductive endocrine axis to aromatase inhibition: I. Data generation in a small fish model

EPA Science Inventory

Adaptive or compensatory responses to chemical exposure can significantly influence in vivo concentration-duration-response relationships. The aim of this study was to provide data to support development of a computational dynamic model of the hypothalamic-pituitary-gonadal axis ...

Cross-Species Conservation of Endocrine Pathways: A Critical Analysis of Tier 1 Fish and Rat Screening Assays with 12 Model Chemicals

EPA Science Inventory

Many structural and functional aspects of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis are known to be highly conserved, but the full significance of this from a toxicological perspective has received comparatively little attention. High-quality data generated throug...

Pituitary disorders in pregnancy.

PubMed

Chrisoulidou, Alexandra; Boudina, Maria; Karavitaki, Niki; Bili, Eleni; Wass, John

2015-01-01

The pituitary gland is significantly affected during gestation in terms of both size and function. Due to this physiologic adaptation, endocrine evaluation and interpretation of imaging is far more complex than in the non-pregnant state. Pituitary disorders are rare in pregnancy, as they are usually associated with gonadal dysfunction, thereby posing difficulties with fertility. This review will focus on pituitary adenomas (prolactinomas, GH-secreting and ACTH-secreting), their diagnostic handicaps and the recommendations for treatment. We will also discuss the two pituitary disorders encountered in pregnancy, Sheehan's syndrome and lymphocytic hypophysitis.

Effects of beta-phenylethylamine on the hypothalamo-pituitary-adrenal axis in the male rat.

PubMed

Kosa, E; Marcilhac-Flouriot, A; Fache, M P; Siaud, P

2000-11-01

beta-Phenylethylamine (PEA) is a trace neuroactive amine implicated in the regulation of the hypothalamic-pituitary-adrenal (HPA) response to stress. To test this hypothesis, effects of subchronic levels of PEA (50 mg/kg/day treatment for 10 days) on the corticotroph function were studied. PEA treatment induces: (i) a significant increase of corticotrophin releasing hormone (CRH) immunoreactivity in the median eminence (ME), as measured by semi-quantitative immunofluorescence labeling techniques, (ii) a significant increase in CRH mRNA levels in paraventricular nuclei, as detected by in situ hybridization, and (iii) an increase in plasma adreno-corticotrophin hormone (ACTH) and corticosterone levels in responses to stress. PEA treatment has no effect on the number of binding sites and on the dissociation constant of the glucocorticoid receptors in any structure studied. Results of the dexamethasone suppression test were similar in PEA- and saline-treated rats. Taken together, these results suggest that PEA treatment stimulated the HPA axis activity levels directly via the CRH hypothalamic neurons, without altering the negative feed back control exerted by the glucocorticoids.

Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System

PubMed Central

Burford, Natalie G.; Webster, Natalia A.; Cruz-Topete, Diana

2017-01-01

The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA) axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart. PMID:29035323

Oxytocin for the treatment of drug and alcohol use disorders.

PubMed

Lee, Mary R; Weerts, Elise M

2016-12-01

There is growing interest in the use of oxytocin (OT) as a potential treatment for alcohol and other substance-use disorders. OT is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. OT exerts its effects through interactions with the hypothalamic-pituitary-adrenal axis and multiple neurotransmitter systems including the dopamine mesolimbic reward and corticotrophin-releasing factor stress systems. The effects of OT on stress systems are of high interest, given the strong link between stress, drug use and relapse, and known dysregulation of hypothalamic-pituitary-adrenal-axis activity associated with substance-use disorders. At the same time, the OT system is itself altered by acute or chronic drug exposure. This review summarizes the preclinical and clinical literature on the OT system and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis, or alcohol use disorder are included and evidence that OT may help to normalize blunted stress responses, and attenuate withdrawal-associated hypercortisolism, negative mood, and withdrawal symptoms is summarized.