The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

PubMed Central

de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

1996-01-01

Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

PubMed

de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

1996-03-01

Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain-cleavage enzyme, P450scc [corrected], in human steroidogenic tissues.

PubMed Central

Voutilainen, R; Miller, W L

1987-01-01

Insulin-like growth factors (IGFs) are single-chain polypeptides important for cell proliferation and growth. IGFs are produced in several tissues, suggesting that they function in a paracrine or autocrine fashion as well as functioning as endocrine hormones. We studied the hormonal regulation of IGF-I and IGF-II mRNA in human steroidogenic tissues. In cultured human ovarian granulosa cells, follicle-stimulating hormone, human chorionic gonadotropin, and dibutyryl cAMP increased IGF-II mRNA, but corticotropin [adrenocorticotropic hormone (ACTH)], chorionic somatomammotropin, growth hormone, prolactin, dexamethasone, estradiol, and progesterone had no effect. In cultured human fetal adrenal cells, ACTH and dibutyryl cAMP increased IGF-II mRNA accumulation, but human chorionic gonadotropin and angiotensin II did not. The same five size species of IGF-II mRNA were detected in transfer blots of RNA from granulosa cells and fetal adrenal cells, and all of these increased after hormonal stimuli. Dibutyryl cAMP also increased IGF-II mRNA accumulation in cultured human placental cells. Accumulation of mRNA for the cholesterol side-chain-cleavage monooxygenase [P450scc [corrected]; cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving), EC 1.14.15.6] was regulated in parallel with IGF-II mRNA in all these steroidogenic tissues. IGF-I mRNA was not detected in transfer blots of these RNAs, and the minimal amounts detected in dot blots showed no detectable change after any of the hormonal stimuli studied. The data indicate that the IGF-II gene is expressed in human steroidogenic tissues and is regulated by cAMP. These data suggest that IGF-II may act in an autocrine or paracrine fashion to stimulate the adrenal and gonadal growth stimulated by ACTH and gonadotropins, respectively. Images PMID:3031644

Corticotropin-releasing factor accelerates metamorphosis in Bufo arenarum: effect on pituitary ACTH and TSH cells.

PubMed

Miranda, L A; Affanni, J M; Paz, D A

2000-04-01

The actions of several neuropeptides as hypothalamic mediators in the regulation of Bufo arenarum metamorphosis were investigated. Prometamorphic larvae were injected with 1.5 microg thyrotropin-releasing hormone (TRH), 2 microg ovine corticotropin-releasing factor (oCRF), 2 microg mammalian gonadotropin-releasing hormone (mGnRH), 2 microg human growth hormone-releasing hormone (hGHRH), or Holtfreter solution (control group). Larvae received two injections with the same dose: one at the beginning of the experiment and the other 7 days later. Several morphologic parameters (total length, tail length, wet weight, hind limb length, and metamorphic stages) were measured as indicators of growth and metamorphic development. These measurements were taken in 20 larvae per treatment or control group at the beginning of the experiment, at day 7 and at day 14 when the experiment ended. We observed that only the administration of exogenous CRF stimulated resorption of the tail and accelerated the rate of metamorphosis. In the pituitary of CRF-treated larvae we observed that thyrotropin (TSH) and adrenocorticotropic hormone (ACTH) producing cells showed a weaker immunoreactivity, a decrease in cell number and a reduction of volume density when compared with normal larvae. In conclusion, the results obtained indicate a possible role for CRF in Bufo arenarum metamorphosis. CRF may regulate interrenal and thyroid activity by acting directly upon TSH and ACTH cells. On the other hand, TRH, GnRH and GHRH were inactive in stimulating growth or metamorphosis of Bufo arenarum. J. Exp. Zool. 286:473-480, 2000. Copyright 2000 Wiley-Liss, Inc.

Radioimmunoassay of ACTH in plasma

PubMed Central

Berson, Solomon A.; Yalow, Rosalyn S.

1968-01-01

Techniques are described in detail for a radioimmunoassay of plasma adrenocorticotropin (ACTH) that is capable of detecting hormone in unextracted normal human plasma at 1:5 dilution under the conditions described. The sensitivity of the assay is at the level of 1 μμg/ml (equivalent to 0.014 mU/100 ml). In normal subjects ACTH concentrations averaged 22 μμg/ml (equivalent to 0.308 mU/100 ml) plasma at 8-10 a.m. In a smaller group the concentrations averaged 9.6 μμg/ml (equivalent to 0.134 mU/100 ml) at 10-11 p.m. Although a circadian rhythm in normal subjects was not always well marked throughout the daytime hours, plasma ACTH usually fell to its lowest value in the late evening. In hospital patients who were not acutely ill, concentrations were infrequently above 100 μμg/ml in the morning and usually fell to significantly lower levels in the late evening. Severely ill hospital patients occasionally exhibited a.m. concentrations above 200 μμg/ml. In a group of subjects showing frequent spiking of plasma 17-OHCS concentrations throughout the day parallel spiking of plasma ACTH as well was generally observed. Metyrapone produced marked increases in plasma ACTH within 24 hr in all cases and generally within 3-6 hr except when started late in the day. Dexamethasone brought about a persistent reduction in plasma ACTH in a patient under continued treatment with metyrapone. Hypoglycemia, electroshock, surgery under general anesthesia, histalog and vasopressin administration were usually followed by significant increases in plasma ACTH concentration. Prior administration of dexamethasone blocked the response to hypoglycemia. Marked elevations in plasma ACTH were observed in patients with adrenal insufficiency off steroid therapy, in Cushing's disease after adrenalectomy even in the presence of persistent hypercortisolemia, and in some untreated patients with Cushing's disease. Umbilical cord blood contained higher plasma ACTH concentrations than maternal blood at

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.

A rare cause of Cushing's syndrome: an ACTH-secreting phaeochromocytoma.

PubMed

Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg; Glintborg, Dorte

2014-10-08

Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH-secreting phaeochromocytoma as the underlying cause of CS. In both cases, female patients presented with the classical clinical signs of CS and an adrenal mass. High ACTH levels raised the suspicion of an ACTH-secreting phaeochromocytoma. The diagnosis was confirmed by urinary catecholamine levels and positive fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) CT (Case 1) and fluorodeoxyglucose PET-CT (Case 2). Both patients were treated with an α-blocker prior to surgical intervention. The two cases underline the importance of thorough diagnostic workup in patients with CS. An ACTH-secreting phaeochromocytoma should be checked for in patients with an adrenal mass and elevated ACTH levels. 2014 BMJ Publishing Group Ltd.

A rare cause of Cushing's syndrome: an ACTH-secreting phaeochromocytoma

PubMed Central

Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg; Glintborg, Dorte

2014-01-01

Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH-secreting phaeochromocytoma as the underlying cause of CS. In both cases, female patients presented with the classical clinical signs of CS and an adrenal mass. High ACTH levels raised the suspicion of an ACTH-secreting phaeochromocytoma. The diagnosis was confirmed by urinary catecholamine levels and positive fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) CT (Case 1) and fluorodeoxyglucose PET-CT (Case 2). Both patients were treated with an α-blocker prior to surgical intervention. The two cases underline the importance of thorough diagnostic workup in patients with CS. An ACTH-secreting phaeochromocytoma should be checked for in patients with an adrenal mass and elevated ACTH levels. PMID:25297883

Growth hormone and prolactin responses to corticotrophin-releasing-hormone in patients with Cushing's disease: a paracrine action of the adenomatous corticotrophic cells?

PubMed

Loli, P; Boccardi, E; Branca, V; Bramerio, M; Barberis, M; Losa, M; Terreni, M T; Lodrini, S; Pollo, B; Vignati, F

1998-10-01

In patients with Cushing's disease multihormonal responses to ovine corticotrophin releasing hormone (oCRH) have been detected in blood from inferior petrosal sinuses. This finding has been explained by co-secretion of other hormones, in addition to ACTH, by the pituitary adenoma itself or by paracrine effects exerted by the adenoma on normal periadenomatous pituitary cells. To assess these hypotheses we compared the presence of a CRH induced GH and/or PRL response during inferior petrosal sinus sampling to the immunohistochemical detection of PRL and GH in adenomatous tissue removed from patients with Cushing's disease. Twenty-two patients with Cushing's disease and two patients with ectopic ACTH syndrome due to a bronchial carcinoid were studied; each patient had undergone preoperative inferior petrosal sinus sampling for diagnostic purposes with determination of GH and PRL in addition to ACTH, before and after administration of oCRH. Immunohistochemical studies for ACTH, GH and PRL detection were carried out on adenomatous tissue removed at surgery in the patients with pituitary dependent Cushing's disease and on the carcinoid tumours from the two patients with ectopic ACTH syndrome. All pituitary adenomas immunostained for ACTH, and four adenomas immunostained for GH or PRL in addition to ACTH. A PRL increase in the inferior petrosal sinus after oCRH administration was found in 11 of 22 patients, but none of their tumours immunostained for PRL. Immunostaining for PRL was found in the pituitary tumours from two patients but in neither patient was there a PRL response after oCRH. A GH response was found in 13 of 20 patients in whom it was sought; no patient showed immunostaining in their tumour. GH immunostaining was found in two tumours but in neither patient was there a GH response after oCRH. The oCRH-induced increase of GH and PRL was always recorded in the dominant inferior petrosal sinus. The ACTH response to oCRH was significantly higher in patients who

Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1980-01-01

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD).

PubMed

Scheidegger, M D; Gerber, V; Bruckmaier, R M; van der Kolk, J H; Burger, D; Ramseyer, A

2017-10-01

This study tested the hypothesis that adrenocortical function would be altered in horses with equine gastric ulcer syndrome (EGUS). Twenty-six sport horses competing at national or international levels in eventing (n=15) or endurance (n=11) were subjected to a gastroscopic examination and an adrenocorticotropic hormone (ACTH) stimulation test. Salivary cortisol concentrations were measured before (baseline) and after (30, 60, 90, 120 and 150min) IV ACTH injection (1μg/kg bodyweight). Within EGUS, two distinct diseases, equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), can be distinguished. ESGD was diagnosed in 8/11 (73%; 95% confidence intervals [95%CI], 43-92%) endurance horses and 5/15 (33%; 95% CI, 14-58%) eventing horses. EGGD was observed in 9/11 (82%; 95% CI, 53-96%) endurance horses and 9/15 (60%; 95% CI, 35-81%) eventing horses. The presence or severity of ESGD was unrelated to the presence or severity of EGGD. ACTH stimulation induced a larger increase in cortisol concentration in horses with moderate EGGD than in horses with mild EGGD. Cortisol concentration during the entire sampling period (total increase in cortisol concentration during the entire sampling period [dAUC], 31.1±6.4ng/mL) and the highest measured concentration at a single time point (maximal increase in cortisol concentration [dMAX], 10.3±2.3ng/mL) were increased (P=0.005 and P=0.038, respectively), indicating that horses with glandular gastric disease exhibited increased adrenocortical responses to ACTH stimulation. These results suggest that EGGD might be associated with an enhanced adrenocortical sensitivity. Further investigations are warranted to confirm the association between adrenocortical sensitivity and EGGD and to elucidate the pathophysiological mechanisms involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas

PubMed Central

Fukuoka, Hidenori; Cooper, Odelia; Ben-Shlomo, Anat; Mamelak, Adam; Ren, Song-Guang; Bruyette, Dave; Melmed, Shlomo

2011-01-01

Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease. PMID:22105169

ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

PubMed

Gorostizaga, Alejandra Beatriz; Mori Sequeiros Garcia, M Mercedes; Acquier, Andrea B; Lopez-Costa, Juan J; Mendez, Carlos F; Maloberti, Paula M; Paz, Cristina

2016-09-01

Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

ACTH Action on StAR Biology

PubMed Central

Clark, Barbara J.

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

ACTH Action on StAR Biology.

PubMed

Clark, Barbara J

2016-01-01

Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells

PubMed Central

Jian, Fang-Fang; Li, Yun-Feng; Chen, Yu-Fan; Jiang, Hong; Chen, Xiao; Zheng, Li-Li; Zhao, Yao; Wang, Wei-Qing; Ning, Guang; Bian, Liu-Guan; Sun, Qing-Fang

2016-01-01

Background: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). Methods: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD. PMID:27569239

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

PubMed

Loche, S; Carta, D; Muntoni, A C; Corda, R; Pintor, C

1993-10-01

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Stimulation of in vitro steroidogenesis by pituitary hormones in a turtle (Trachemys scripta) within the temperature-sensitive period for sex determination.

PubMed

White, R B; Thomas, P

1992-12-01

To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

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

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitorymore » effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.« less

Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

PubMed Central

PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

2016-01-01

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

Muscle transcriptome response to ACTH administration in a free-ranging marine mammal

PubMed Central

Champagne, Cory D.; Preeyanon, Likit; Ortiz, Rudy M.; Crocker, Daniel E.

2015-01-01

While much of our understanding of stress physiology is derived from biomedical studies, little is known about the downstream molecular consequences of adaptive stress responses in free-living animals. We examined molecular effectors of the stress hormones cortisol and aldosterone in the northern elephant seal, a free-ranging study system in which extreme physiological challenges and cortisol fluctuations are a routine part of life history. We stimulated the neuroendocrine stress axis by administering exogenous adrenocorticotropic hormone (ACTH) and examined the resultant effects by measuring corticosteroid hormones, metabolites, and gene expression before, during, and following administration. ACTH induced an elevation in cortisol, aldosterone, glucose, and fatty acids within 2 h, with complete recovery observed within 24 h of administration. The global transcriptional response of elephant seal muscle tissue to ACTH was evaluated by transcriptomics and involved upregulation of a highly coordinated network of conserved glucocorticoid (GC) target genes predicted to promote metabolic substrate availability without causing deleterious effects seen in laboratory animals. Transcriptional recovery from ACTH was characterized by downregulation of GC target genes and restoration of cell proliferation, metabolism, and tissue maintenance pathways within 24 h. Differentially expressed genes included several adipokines not previously described in muscle, reflecting unique metabolic physiology in fasting-adapted animals. This study represents one of the first transcriptome analyses of cellular responses to hypothalamic-pituitary-adrenal axis stimulation in a free-living marine mammal and suggests that compensatory, tissue-sparing mechanisms may enable marine mammals to maintain cortisol and aldosterone sensitivity while avoiding deleterious long-term consequences of stress. PMID:26038394

[Growth hormone treatment update].

PubMed

2014-02-01

Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

NASA Technical Reports Server (NTRS)

Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, E. G.; Lyapina, L. A.

1980-01-01

The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin.

Growth hormone stimulation test

MedlinePlus

... Philadelphia, PA: Elsevier Saunders; 2016:chap 23. Chernecky CC, Berger BJ. Growth hormone (somatotropin, GH) and growth hormone-releasing hormone (GHRH) - blood. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures . ...

Growth hormone deficiency - children

MedlinePlus

... be done include: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 ( ... C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, ...

Influence of E. coli endotoxin on ACTH induced adrenal cell steroidogenesis.

PubMed

Garcia, R; Viloria, M D; Municio, A M

1985-03-01

The effect of endotoxin (lipopolysaccharide from E. coli) on isolated adrenocortical cells was examined. Lipopolysaccharide decreased the ACTH-induced steroidogenesis. This effect was shown by all corticotropin concentrations studied, and the longer the incubation time, the higher the effect produced. The rate of decrease of ACTH-induced steroidogenesis was dependent on the concentration of lipopolysaccharide in the medium. Binding of [125I]ACTH to adrenocortical cells was modified by lipopolysaccharide; this modification was related to a decrease of the ACTH-induced steroidogenesis. This effect supports the hypothesis of a direct interaction between lipopolysaccharide and the cell membrane with a concomitant distortion of the cell surface affecting the ACTH receptor sites of their environment. [14C]Lipopolysaccharide binds to isolated adrenocortical cells. Binding specificity was investigated by competitive experiments in the presence of various types of endotoxins, polypeptide hormones and proteins. Unlabelled lipopolysaccharide from the same bacterial strain and isolated under identical conditions than the labelled lipopolysaccharide exerted the strongest inhibitory activity. Unlabelled lipopolysaccharide of various strains different from that originating the labelled lipopolysaccharide exerted the less displacement. It would imply a certain kind of specificity but the decrease in the binding of lipopolysaccharide produced by ACTH and glucagon suggests the existence of non-specific interactions between lipopolysaccharide and cell membrane.

The growth hormone cascade: progress and long-term results of growth hormone treatment in growth hormone deficiency.

PubMed

Grumbach, M M; Bin-Abbas, B S; Kaplan, S L

1998-01-01

The growth hormone (GH) cascade and the remarkable advances over the past four decades in our knowledge of its components are considered. It is now over 40 years since human pituitary GH (pit-hGH) was purified and the first GH-deficient patient, a 17-year-old male, was successfully treated with pit-hGH. However, the shortage of pit-hGH limited its use and the dose, the biopotency of preparations varied, strict criteria of GH deficiency (GHD) were used for patient selection including peak plasma immunoreactive GH levels after provocative stimuli of <3.5-5 ng/ml, treatment was not infrequently interrupted, the mean age for initiating treatment was often late in childhood (12-13 years) and the growth deficiency severe (height -4 to -6 SDS), and finally pit-hGH therapy was often discontinued when girls attained a height of 5' and boys 5'5". Nonetheless, the effects of pit-hGH were dramatic; the final height SDS increased in isolated GHD to about -2 SDS in boys and -2.5 to -3.0 SDS in girls, and in multiple pituitary hormone deficiencies to between -1 and -2 SDS. Between 1962 and 1985 when the Creutzfeldt-Jakob disease crisis struck, the number of GH-deficient patients treated with pit-hGH increased from about 150 to over 3,000. The advent of biosynthetic GH (rhGH) and its availability to treat large numbers of idiopathic GH-deficient children (the minimum prevalence rate of which in the USA and UK is between 1 in 3,400 and 4,000) dramatically changed this picture in 1985. It is estimated that more than 60,000 patients have been or are now on treatment. With rhGH treatment the attained mean adult height SDS is now about -1.0, and in our experience with the treatment of patients under 4 years of age, final height may exceed the target height. It is now recognized that (a) the replacement dose of rhGH ranges from 0.175 to 0.35 mg/kg/week and should be individualized; (b) dividing this dose into 6 or 7 daily subcutaneous injections is more effective than giving the same

Comparative Effects of Angiotensin and ACTH on Cyclic AMP and Steroidogenesis in Isolated Bovine Adrenal Cells

PubMed Central

Peytremann, Andre; Nicholson, Wendell E.; Brown, Ronald D.; Liddle, Grant W.; Hardman, Joel G.

1973-01-01

The comparative effects of angiotensin II and adrenocorticotropic hormone (ACTH) on cyclic AMP and steroidogenesis were investigated employing isolated bovine adrenal cells from the zona fasciculata. Like ACTH, angiotensin produced a prompt increase in cyclic AMP which preceded the increase in corticosteroid production. Although this increase in cyclic AMP was small when compared to that induced by ACTH, it correlated with the amount of steroidogenesis. This observation is consistent with the view that cyclic AMP is the intracellular mediator of the steroidogenic action of angiotensin. Angiotensin acted synergistically with ACTH on cyclic AMP levels. This synergism was not explained by inhibition of phosphodiesterase activity. Unlike ACTH, angiotensin failed to stimulate adenylate cyclase in broken cell preparations. The observations suggest that more than one mechanism may be involved in effects of ACTH and angiotensin on cyclic AMP levels. PMID:4348344

Growth hormone in intra-uterine growth retarded newborns.

PubMed

Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Latha

2007-11-01

To study growth hormone levels in IUGR and healthy controls and its association with birth weight and ponderal index. We studied 50 Intra uterine growth retarded (IUGR) and 50 healthy newborns born at term by vaginal delivery in JIPMER, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of growth hormone. When compared with healthy newborns, IUGR newborns had higher growth hormone levels (mean +/- SD, 23.5 +/- 15.6 vs 16.2 +/- 7.61 ngm/ml, P = 0.019). A negative correlation was identified between growth hormone levels and birth weight (r2 = - 0.22, P = 0.03) and ponderal index (r2 = - 0.36, P = 0.008). Correlation of growth hormone levels was much more confident with ponderal index than with birth weight. At birth IUGR infants display increased growth hormone levels which correlate with ponderal index much more confidently than with birth weight.

A nonpeptidyl growth hormone secretagogue.

PubMed

Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

1993-06-11

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?

PubMed

Gobbi, Giuseppe; Loiacono, Giulia; Boni, Antonella; Marangio, Lucia; Verrotti, Alberto

2014-06-01

Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.

Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

PubMed Central

Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

2015-01-01

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

[Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats].

PubMed

Sever'ianova, L A

1977-01-01

In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres.

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

PubMed

Dos Santos, Christine; Essioux, Laurent; Teinturier, Cécile; Tauber, Maïté; Goffin, Vincent; Bougnères, Pierre

2004-07-01

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.

HYDROCORTISONE THERAPY AND GROWTH TRAJECTORY IN CHILDREN WITH CLASSICAL CONGENITAL ADRENAL HYPERPLASIA.

PubMed

Bizzarri, Carla; Improda, Nicola; Maggioli, Chiara; Capalbo, Donatella; Roma, Silvia; Porzio, Ottavia; Salerno, Mariacarolina; Cappa, Marco

2017-05-01

Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations. Height velocity, pubertal growth spurt, and final height were evaluated as outcomes. Final height standard deviation score (SDS) was lower than target height SDS (-0.74 ± 1.1 versus -0.31 ± 1.01; P<.001). Target-adjusted final height SDS was -0.44 ± 1.8 in males and -0.13 ± 1.1 in females (P = .001). Total pubertal growth was 21.9 ± 7.3 cm in males and 19.2 ± 8.2 cm in females (P = .19). Hydrocortisone dose increased and height-velocity SDS decreased during puberty. At multivariable analysis, height-velocity SDS was adversely affected by hydrocortisone dose (P = .038) and directly related to adrenocorticotropic hormone (ACTH) levels (P = .023). Target-adjusted final-height SDS was adversely affected by hydrocortisone dose (P<.001) and positively related to mineralocorticoid therapy (P = .001) and ACTH levels (P = .02). Total pubertal growth (cm) was positively related to ACTH levels (P = .01). Height outcome of CAH patients is now better than previously reported. During puberty, the lowest effective dose of hydrocortisone should be used to optimize pubertal growth spurt and final height. 17-OHP = 17-alpha-hydroxyprogesterone ACTH = adrenocorticotropic hormone BMI = body mass index CAH = congenital adrenal hyperplasia GH = growth hormone HPA = hypothalamus-pituitary-adrenal PRA = plasma renin activity SDS = standard deviation score SV = simple virilizing SW = salt-wasting.

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

Hormonal Control of Fetal Growth.

ERIC Educational Resources Information Center

Cooke, Paul S.; Nicoll, Charles S.

1983-01-01

Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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

Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

Motion sickness susceptibility related to ACTH, ADH and TSH

NASA Technical Reports Server (NTRS)

Kohl, R. L.; Leach, C.; Homick, J. L.; Larochelle, F. T.

1983-01-01

The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

Regulation of fish growth hormone transcription.

PubMed

Farchi-Pisanty, O; Hackett, P B; Moav, B

1995-09-01

Regulation of endogenous fish growth hormone transcription was studied using carp pituitaries in vitro. It was demonstrated that thyroid hormone (T3) and 9-cis retinoic acid have increased the steady state levels of growth hormone messenger RNA in pituitary cells, as compared with beta-actin messenger RNA levels. In contrast, estrogen failed to increase growth hormone mRNA levels. The possible involvement of thyroid hormone receptor in pituitary gene expression was demonstrated by in situ localization of both growth hormone mRNA and thyroid hormone receptor mRNA in the pituitaries as early as 4 days after fertilization.

[Therapy with recombinant growth hormone].

PubMed

Wabitsch, Martin

2007-06-07

Therapy with recombinant growth hormone is currently approved for the indications growth hormone deficiency,Turner syndrome, chronic renal failure, small for gestational age (SGA) and Prader-Willi syndrome. Positive experience from on-going clinical studies (e.g. on obesity, type 2 diabetes, Crohn's disease) support an extended range of applications for recombinant growth hormone. However, growth hormone therapy is very expensive. On the other hand, biosimilars are already available that are significantly lower in price. During the coming years, research must show whether the efficacy and safety of biosimilars (including possible new indications) are equal to that of the established preparations.

Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

PubMed

Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

2003-09-01

Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

Ionic dependence of adrenal steroidogenesis and ACTH-induced changes in the membrane potential of adrenocortical cells

PubMed Central

Matthews, E. K.; Saffran, M.

1973-01-01

1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output. 2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution. 3. The steroidogenic response to ACTH was not impaired after omission of [K]o for 1 hr but was inhibited following exposure to K+-free medium for 3 hr. Increase of [K]o tenfold to 47 mM increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K]o twentyfold to 94 mM enhanced both the basal and ACTH-stimulated steroid production rate. In K+-free solution the adrenocortical cells hyperpolarized from - 67 to - 86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K+ restored the membrane potential. 4. Omission of Ca2+ partially depolarized the cells but only affected the steroidogenic response to ACTH in the presence of EDTA. A threefold increase of [Ca]o, to 7·68 mM, had no effect on either membrane potentials or steroid formation, but increasing [Ca]o tenfold to 25·6 mM partially blocked ACTH action. Increasing [Mg]o twentyfold to 22·6 mM had little effect on ACTH-stimulated corticosteroid output and Sr 2·56 mM, in substitution for Ca2+, supported ACTH action, but La, 0·25 mM, completely blocked the steroidogenic effect of ACTH. 5. Replacement of NaCl, 118 mM by choline chloride, 118 mM, was without effect on ACTH-induced steroidogenesis, whereas LiCl, 118 mM, reduced it by 50%. NaF, 1 and 10 mM, inhibited ACTH-induced steroidogenesis by approximately 60%. 6. Nupercaine, 10-4 M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine

Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

USGS Publications Warehouse

Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel N.; Mulcahy, D.M.; Rizzolo, D.J.

2008-01-01

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.

Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

PubMed

Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

2013-11-01

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.

PubMed

Rydzewska, Marta; Krawczuk-Rybak, Maryna; Zajkowska, Adrianna; Jurczuk, Natalia; Polnik, Dariusz; Szalecki, Mieczysław; Moszczyńska, Elżbieta; Savage, Martin O; Bossowski, Artur

2017-04-01

Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.

Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

ERIC Educational Resources Information Center

Pueschel, Seigfried M.

1993-01-01

This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone) during Inferior Petrosal Sinus Sampling.

PubMed

Carroll, Ty B; Fisco, Amy J H; Auchus, Richard J; Kennedy, Laurence; Findling, James W

2014-07-01

The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS. We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS. In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration. An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.

[Hormones and hair growth].

PubMed

Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

Central neuropeptide B administration activates stress hormone secretion and stimulates feeding in male rats.

PubMed

Samson, W K; Baker, J R; Samson, C K; Samson, H W; Taylor, M M

2004-10-01

Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the orphan receptors GPR7 and GPR8. Because GPR7 is expressed in rat brain and, in particular, in the hypothalamus, we hypothesized that NPB might interact with neuroendocrine systems that control hormone release from the anterior pituitary gland. No significant effects of NPB were observed on the in vitro releases of prolactin, adrenocorticotropic hormone (ACTH) or growth hormone (GH) when log molar concentrations ranging from 1 pM to 100 nM NPB were incubated with dispersed anterior pituitary cells harvested from male rats. In addition NPB (100 nM) did not alter the concentration response stimulation of prolactin secretion by thyrotropin-releasing hormone, ACTH secretion by corticotropin-releasing factor (CRF) and GH secretion by GH-releasing hormone. However, NPB, when injected into the lateral cerebroventricle (i.c.v.) of conscious, unrestrained male rats, elevated prolactin and corticosterone, and lowered GH levels in circulation. The threshold dose for the effect on corticosterone and prolactin levels was 1.0 nmol, while that for the effect on GH release was 3.0 nmol NPB. Pretreatment with a polyclonal anti-CRF antiserum completely blocked the ability of NPB to stimulate ACTH release and significantly inhibited the effect of NPB on plasma corticosterone levels. NPB administration i.c.v. did not significantly alter plasma vasopressin and oxytocin levels in conscious rats. It did stimulate feeding (minimum effective dose 1.0 nmol) in sated animals in a manner similar to that of the other endogenous ligand for GPR7, neuropeptide W. We conclude that NPB can act in the brain to modulate neuroendocrine signals accessing the anterior pituitary gland, but does not itself act as a releasing or inhibiting factor in the gland, at least with regard to prolactin, ACTH and GH secretion.

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing's Disease to Pituitary Carcinoma.

PubMed

Borba, Clarissa Groberio; Batista, Rafael Loch; Musolino, Nina Rosa de Castro; Machado, Vanielle Carvalho; Alcantara, Ana Elisa Evangelista; da Silva, Gilberto Ochman; Sperling Cescato, Valter Angelo; da Cunha Neto, Malebranche Berardo Carneiro

2015-01-01

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing's disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Human growth hormone induced cholestatic hepatitis in a growth hormone deficient patient with short stature.

PubMed

Zahmatkeshan, Mozhghan; Karamizadeh, Zohre; Geramizadeh, Bita; Eshraghian, Ahad

2014-03-01

We report a patient with growth hormone deficiency that developed cholestatic hepatitis during treatment with recombinant human growth hormone (HGH). The patient developed jaundice and pruritus during treatment with growth hormone. She did not use any other medications. Her jaundice and pruritus were disappeared and liver enzyme disturbances were normalized after HGH discontinuation. Clinician should be aware of this potential adverse drug reaction and frequent checking of liver enzymes is recommended in patients treating with HGH.

UTILITY OF A SINGLE LATE-NIGHT PLASMA CORTISOL AND ACTH FOR THE DIAGNOSIS OF CUSHING SYNDROME.

PubMed

Jarial, Kush Dev Singh; Bhansali, Anil; Mukherjee, Kanchan K; Pal, Rimesh; Sharma, Akhilesh; Vashishtha, Rakesh K; Sukumar, Suja P; Sachdeva, Naresh; Walia, Rama

2018-02-01

To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS). Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission. We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 μg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively. UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS. ACTH = adrenocorticotropic hormone AUC = area under the curve CRH = corticotropin-releasing hormone CS = Cushing syndrome ECLIA = electrochemiluminescence immuno-assay LDDST = low-dose dexamethasone suppression test LNPC = late-night plasma cortisol LNSC = late-night salivary cortisol ONDST = overnight dexamethasone suppression

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

USDA-ARS?s Scientific Manuscript database

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

A simple and cost-effective approach to assessment of pituitary adrenocorticotropin and growth hormone reserve: combined use of the overnight metyrapone test and insulin-like growth factor-I standard deviation scores.

PubMed

Gibney, James; Healy, Marie-Louise; Smith, Thomas P; McKenna, T Joseph

2008-10-01

The insulin tolerance test (ITT) is the gold standard for assessment of ACTH and GH reserve in patients with suspected hypopituitarism. It is labor intensive and costly. The objective of the study was to determine whether use of the overnight metyrapone test (OMT) and plasma IGF-I sd scores (SDS) could provide a cost-effective alternative to the ITT. This was a retrospective chart review. The study was conducted at a teaching hospital. Charts from 100 patients with organic pituitary disorders were reviewed. All underwent the OMT unless 0900 h plasma cortisol was less than 80 or greater than 450 nmol/liter when ACTH deficiency or ACTH sufficiency, respectively, was diagnosed. Patients were considered GH deficient if the age-related IGF-I SDS was less than -3 or if they had three or more other pituitary hormone deficiencies. Patients were considered GH sufficient if age-related IGF-I SDS was greater than the 95th centile established from patients with known GH deficiency. Thirty-three underwent an ITT. The proportion of patients in whom ACTH and GH reserve could be assessed using OMT/IGF-I SDS was measured. The concordance with results was obtained from ITT. Fifty-five patients were ACTH sufficient and 45 were ACTH deficient. Twenty-one were GH sufficient and 33 were GH deficient based on IGF-I SDS and other pituitary hormone deficiencies, whereas 46 could not be classified. There was near-uniform concordance between OMT/IGF-I SDS and ITT. Initial investigation using OMT/IGF-I SDS resulted in a significant cost saving. ACTH and GH reserve can be accurately and cost-effectively investigated using OMT/IGF-I SDS in approximately 50% of patients with organic pituitary disorders.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

PubMed

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-04-25

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

PubMed Central

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-01-01

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

PubMed Central

Si, Jin; Ge, Yan; Zhuang, Shougang; Juan Wang, Li; Chen, Shan; Gong, Rujun

2013-01-01

Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)–induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture–induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI. PMID:23325074

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats.

PubMed

Perelló, Mario; Chacon, Fernando; Cardinali, Daniel P; Esquifino, Ana I; Spinedi, Eduardo

2006-03-13

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Role of Growth Hormone in Breast Cancer.

PubMed

Subramani, Ramadevi; Nandy, Sushmita B; Pedroza, Diego A; Lakshmanaswamy, Rajkumar

2017-06-01

Breast cancer is one of the most common cancers diagnosed in women. Approximately two-thirds of all breast cancers diagnosed are classified as hormone dependent, which indicates that hormones are the key factors that drive the growth of these breast cancers. Ovarian and pituitary hormones play a major role in the growth and development of normal mammary glands and breast cancer. In particular, the effect of the ovarian hormone estrogen has received much attention in regard to breast cancer. Pituitary hormones prolactin and growth hormone have also been associated with breast cancer. Although the role of these pituitary hormones in breast cancers has been studied, it has not been investigated extensively. In this review, we attempt to compile basic information from most of the currently available literature to understand and demonstrate the significance of growth hormone in breast cancer. Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance. Copyright © 2017 Endocrine Society.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

PubMed

Barbot, Mattia; Trementino, Laura; Zilio, Marialuisa; Ceccato, Filippo; Albiger, Nora; Daniele, Andrea; Frigo, Anna Chiara; Mardari, Rodica; Rolma, Giuseppe; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

2016-10-01

Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Influence of a prenatal stressor on ACTH-induced cortisol secretion in yearling Brahman heifers

USDA-ARS?s Scientific Manuscript database

The objective of this study was to test whether prenatal stress affects postnatal adrenocortical responsiveness to exogenous adrenocorticotropin-releasing hormone (ACTH) in calves of Brahman cows transported for 2-hour periods at 60, 80, 100, 120, and 140 days of gestation. Prenatally stressed yearl...

[Human growth hormone and Turner syndrome].

PubMed

Sánchez Marco, Silvia Beatriz; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José Ignacio; Garagorri Otero, Jesús María

2017-02-01

The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

A hormone map of human immune cells showing the presence of adrenocorticotropic hormone, triiodothyronine and endorphin in immunophenotyped white blood cells

PubMed Central

Pállinger, Éva; Csaba, György

2008-01-01

The amounts of adrenocorticotropic hormone (ACTH), endorphin and triiodothyronine (T3) in twenty-six blood samples from men and women who were healthy or had non-haematological diseases were determined by flow cytometry. Lymphocytes were immunophenotyped using monoclonal antibodies against cell surface antigens, and monocytes and granulocytes were separated by their size and granularity (using forward-scatter versus side-scatter dot plots). Each hormone was found in each cell type. The hormone content of lymphocytes was balanced, but the concentration of ACTH was significantly lower in activated T cells, that of endorphin was significantly lower in natural killer (NK) cells, and that of T3 was lower in both cell types compared with values for all lymphocytes. Monocytes and granulocytes contained very significantly more hormones than lymphocytes or monocytes. The concentration of endorphin was an order of magnitude higher in granulocytes than in monocytes or lymphocytes, reflecting the pain-relieving role of granulocytes during inflammation. Compared with monocytes, in granulocytes there was a higher concentration of ACTH and a lower concentration of T3, which suggests selective hormone production by these cells. PMID:18005034

ACTH Antibodies in Patients Receiving Depot Porcine ACTH to Hasten Recovery from Pituitary-Adrenal Suppression*

PubMed Central

Fleischer, Norman; Abe, Kaoru; Liddle, Grant W.; Orth, David N.; Nicholson, Wendell E.

1967-01-01

Six patients who had experienced prolonged steroid-induced pituitary-adrenal suppression were treated with 100 U of depot procine ACTH every 2 to 4 days for several months. Such treatment did not hasten the recovery of normal pituitary-adrenal function compared with the rate of recovery of a group of similarly suppressed patients who received no depot ACTH. Eight of nine patients who received prolonged courses of depot porcine ACTH developed antibodies to ACTH that cross-reacted with endogenous ACTH, binding it in the circulation in inactive form and retarding its removal from the circulation. The presence of such antibodies did not in itself grossly alter pituitary-adrenal interrelationships. Images PMID:4289551

Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

PubMed Central

Farthing, M J; Campbell, C A; Walker-Smith, J; Edwards, C R; Rees, L H; Dawson, A M

1981-01-01

Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five patients, five hour mean growth hormone levels were reduced (3.8, 5.0, and 8.5 mU/l) compared with levels reported previously in normal short children (10-43 mU/l), although the pulsatile pattern of growth hormone secretion was preserved in all. Nocturnal growth hormone secretion was unrelated to the growth velocities of these children during both pre- and post-treatment assessment periods but a significant correlation was found between growth hormone concentration and a disease activity score (r = 0.79, P less than 0.05), suggesting that growth hormone release by the pituitary was influenced by the severity of the disease. Nocturnal growth hormone secretion was also correlated with gonadotrophin secretion (luteinising hormones, r = 0.99, and follicle stimulating hormone, r = 0.96; p less than 0.01) indicating more extensive hypothalamic-pituitary disturbance. These findings suggest that hypothalamic-pituitary function is depressed in growth retarded children with Crohn's disease, but that abnormalities of growth hormone secretion are unlikely to be directly involved in the growth retardation seen in this condition. PMID:7308847

Interactions between the thyroid hormones and the hormones of the growth hormone axis.

PubMed

Laron, Zvi

2003-12-01

The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

PubMed Central

Leite de Oliveira, Felipe; Soares, Nathália; de Mattos, Rômulo Medina; Hecht, Fábio; Dezonne, Rômulo Sperduto; Vairo, Leandro; Goldenberg, Regina Coeli dos Santos; Gomes, Flávia Carvalho Alcântara; de Carvalho, Denise Pires; Gadelha, Mônica R.; Nasciutti, Luiz Eurico; Miranda-Alves, Leandro

2013-01-01

Pituitary adenomas comprise approximately 10–15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease. PMID:23667519

Three-week combination treatment with ACTH + magnesium sulfate versus ACTH monotherapy for infantile spasms: a 24-week, randomized, open-label, follow-up study in China.

PubMed

Zou, Li-Ping; Wang, Xu; Dong, Chang-Hong; Chen, Chun-Hong; Zhao, Wei; Zhao, Ruo-Yan

2010-04-01

Infantile spasms (IS) is an age-specific and severe epileptic encephalopathy that occurs in infancy and early childhood and is usually refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the treatment of choice for IS, but ACTH use has been associated with infection and hypertension. Magnesium ion is an N-methyl-D-aspartic acid (NMDA)-noncompetitive antagonist that might inhibit NMDA activity and has antiepileptic and neuroprotective effects. This study compared the efficacy and tolerability of ACTH + magnesium sulfate (MgSO(4)) versus ACTH monotherapy for the treatment of IS. This 24-week, randomized, open-label follow-up study enrolled male and female infants with IS. Patients were randomly assigned to receive ACTH 25 U/d + MgSO(4) 0.25 g/kg/d, or ACTH 25 U/d only (control), intravenously for 3 weeks. Efficacy was assessed over a period of 24 weeks based on seizure frequency, EEG, and Gesell testing of psychomotor skills (subscales: language, motor, adaptive, and personal-social skills; measured using a developmental quotient [DQ] ). Tolerability was assessed by monitoring for adverse events using laboratory analysis and clinical evaluation. Thirty-eight infants were enrolled (23 male, 15 female; median age, 9.2 months; 19 patients per group). At 12 weeks, 14 patients (73.7%) who received ACTH + MgSO(4) and 9 patients (47.4%) in the control group were seizure free. At 24 weeks, seizure-free rates were 12 (63.2%) in the ACTH + MgSO(4) group and 10 (52.6%) in the control group. On EEG, 9 patients (47.4%) in the ACTH + MgSO(4) group achieved complete recovery (normalized EEG), 5 (26.3 %) attained partial improvement (multifocal spike wave), and 5 (26.3%) had no improvement (hypsarrhythmia or modified hypsarrhythmia). At 4 weeks, in the control group, 5 patients (26.3 %) achieved complete recovery, 6 (31.6%) achieved partial improvement, and 8 (42.1%) had no improvement. Of the 12 patients who were seizure free at 24 weeks in

21 CFR 862.1370 - Human growth hormone test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth hormone...

21 CFR 862.1370 - Human growth hormone test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth hormone...

Growth Hormone and Craniofacial Tissues. An update

PubMed Central

Litsas, George

2015-01-01

Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

PubMed

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is

Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes

PubMed Central

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID

Modulation of adrenocorticotrophin hormone (ACTH)-induced expression of stress-related genes by PUFA in inter-renal cells from European sea bass (Dicentrarchus labrax).

PubMed

Montero, Daniel; Terova, Genciana; Rimoldi, Simona; Tort, Lluis; Negrin, Davinia; Zamorano, María Jesús; Izquierdo, Marisol

2015-01-01

Dietary fatty acids have been shown to exert a clear effect on the stress response, modulating the release of cortisol. The role of fatty acids on the expression of steroidogenic genes has been described in mammals, but little is known in fish. The effect of different fatty acids on the release of cortisol and expression of stress-related genes of European sea bass (Dicentrarchus labrax) head kidney, induced by a pulse of adenocorticotrophin hormone (ACTH), was studied. Tissue was maintained in superfusion with 60 min of incubation with EPA, DHA, arachidonic acid (ARA), linoleic acid or α-linolenic acid (ALA) during 490 min. Cortisol was measured by RIA. The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real-time RT-PCR. There was an effect of the type of fatty acid on the ACTH-induced release of cortisol, values from ALA treatment being elevated within all of the experimental period. The expression of some steroidogenic genes, such as the steroidogenic acute regulatory protein (StAR) and c-fos, were affected by fatty acids, ALA increasing the expression of StAR after 1 h of ACTH stimulation whereas DHA, ARA and ALA increased the expression of c-fos after 20 min. ARA increased expression of the 11β-hydroxylase gene. Expression of heat shock protein 70 (HSP70) was increased in all the experimental treatments except for ARA. Results corroborate previous studies of the effect of different fatty acids on the release of cortisol in marine fish and demonstrate that those effects are mediated by alteration of the expression of steroidogenic genes.

ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase

PubMed Central

2013-01-01

Background Adrenal Cushing’s syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro. Methods In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were determined in the adrenal tissues. Results Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. AVP and metoclopramide were the most prevalent hormonal stimuli triggering positive responses in vivo. Catecholamines induced short-term cortisol production more often in AIMAH cultures compared to other adrenal cells. Short- and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP also increased steroidogenic enzyme mRNA expression, among which an aberrant induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced stimulation of CYP11B1. Conclusions Multiple hormonal signals can simultaneously induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and expression of its type 1a receptor was aberrantly linked to CYP11B1 expression. PMID:24034279

Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players.

PubMed

Schmikli, Sándor L; de Vries, Wouter R; Brink, Michel S; Backx, Frank Jg

2012-11-01

To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Sporting field and sports medical laboratory. Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.

Growth Hormone Studies in Growth Retardation—Therapeutic Response to Administration of Androgen

PubMed Central

Deller, John J.; Plunket, Daniel C.; Forsham, Peter H.

1966-01-01

Growth hormone assays were performed before and after androgen administration in a 12-year-old boy with unexplained growth retardation. A subnormal growth hormone secretion in response to a standard hypoglycemic stimulus was demonstrated, and it was corrected by androgen pretreatment. After that, a normal serum growth hormone level and a temporary growth spurt were demonstrated. ImagesFigure 1. PMID:5942009

Hormones and Human and Nonhuman Primate Growth.

PubMed

Bernstein, Robin Miriam

2017-01-01

The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

Growth Hormone

MedlinePlus

... for Targeted Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol Heavy Metals Helicobacter pylori ... is then given a standard glucose solution (usually 100 grams of glucose) to drink. Blood samples are drawn ...

Measurement of salivary aldosterone: validation by low-dose ACTH test and gender differences.

PubMed

Hlavacova, N; Kerlik, J; Radikova, Z; Izakova, L; Jezova, D

2013-10-01

The aim of the present study was to validate the feasibility of measurement of the salivary aldosterone concentrations by performing a low-dose adrenocorticotropic hormone (ACTH) test. Moreover, the presence of gender differences in salivary aldosterone, considering the phase of the menstrual cycle in women, was verified. The sample consisted of 107 volunteers (60 men, 21 women in the follicular phase and 26 women in the luteal phase of the menstrual cycle). Saliva samples were taken by the subjects themselves around 08:00 AM, at least 60 min after awaking. A separate group of female subjects in the follicular phase underwent low-dose ACTH test (1µg synthetic ACTH i.v.) performed at 08:30 AM with blood and saliva sampling every 30 min for 120 min. Modification of the commercial aldosterone radioimmunoassay methodology for the salivary aldosterone measurement was performed. Salivary aldosterone concentrations rose in response to low-dose ACTH test and positive significant correlation in aldosterone concentrations between plasma and saliva was found. The results showed that women in the luteal phase of the menstrual cycle exhibited significantly higher morning concentrations in salivary aldosterone than men and women in the follicular phase. This study clearly demonstrates suitability of measurement of salivary aldosterone concentrations in the low-dose ACTH test and reveals gender differences in salivary aldosterone levels. The results show high validity of the presented method and its usefulness for assessment of the aldosterone concentrations in saliva.

Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk.

PubMed

Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno

2014-01-01

We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.

Thyroid Hormones and Growth in Health and Disease

PubMed Central

Tarım, Ömer

2011-01-01

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

Growth hormone test

MedlinePlus

... under the skin) Infection (a slight risk any time the skin is broken) Alternative Names GH test Images Growth hormone stimulation test - series References Ali O. Hyperpituitarism, tall stature, and overgrowth ...

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs.

PubMed

Jankord, Ryan; Ganjam, Venkataseshu K; Turk, James R; Hamilton, Marc T; Laughlin, M Harold

2008-06-01

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo-pituitary-adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16-20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted

Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs

PubMed Central

Jankord, Ryan; Ganjam, Venkataseshu K.; Turk, James R.; Hamilton, Marc T.; Laughlin, M. Harold

2009-01-01

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo–pituitary–adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16–20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the

[Excessive growth and growth hormone deficiency after treatment for craniopharyngioma].

PubMed

López Siguero, J P; García García, E; Martínez-Aedo, M J; Martínez Valverde, A

2000-07-01

Some children grow normally or excessively after extirpation of a craniopharyngioma, despite growth hormone deficiency. We report a 4-year-old girl with suprasellar craniopharyngioma. Removal of the tumor resulted in panhypopituitarism. For the next 5 years growth continued at a rate of 8.4-10.6 cm/year and then decreased progressively to 1.2 cm/year. Administration of growth hormone increased growth rate to 9.3 cm/year.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

PubMed

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth?

PubMed Central

Devesa, Jesús; Almengló, Cristina; Devesa, Pablo

2016-01-01

In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown. PMID:27773998

[Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

PubMed

Vyshnevs'ka, O A; Bol'shova, O V

2013-06-01

Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing's syndrome.

PubMed

Castinetti, F; Morange, I; Dufour, H; Jaquet, P; Conte-Devolx, B; Girard, N; Brue, T

2007-09-01

Corticotropin-releasing hormone (CRH)-stimulated petrosal sinus sampling is currently the gold standard method for the differential diagnosis between pituitary and ectopic ACTH-dependent Cushing's syndrome. Our objective was to determine sensitivity and specificity of desmopressin test during petrosal sinus sampling. Forty-three patients had petrosal sinus sampling because of the lack of visible adenoma on magnetic resonance imaging (MRI) and/or because of discordant cortisol response to high-dose dexamethasone suppression test. ACTH sampling was performed in an antecubital vein, right and left petrosal sinuses, then at each location 5 and 10 min after injection of desmopressin. Diagnosis was based on the ACTH ratio between petrosal sinus and humeral vein ACTH after desmopressin test. Diagnosis was confirmed after surgery. A receiver operating characteristics curve was used to determine optimal sensitivity and specificity. Thirty-six patients had Cushing's disease (CD) and seven had ectopic ACTH secretion. A ratio > 2 after desmopressin was found in 35 of the 36 cases of CD (sensitivity: 95%). A ratio < or = 2 was found in the seven patients with ectopic ACTH secretion (specificity: 100%). Sinus sampling was ineffective in determining the left or right localization of the adenoma (sensitivity = 50%). No major adverse effects were observed during or after the procedure. Desmopressin test during petrosal sinus sampling is a safe and effective diagnostic procedure in ACTH-dependent Cushing's syndrome. It thus represents a valuable alternative to CRH.

Effect of Tyr-MIF-1 peptides on blood ACTH and corticosterone concentration induced by three experimental models of stress.

PubMed

Bocheva, A; Dzambazova, E; Hadjiolova, R; Traikov, L; Mincheva, R; Bivolarski, I

2008-10-01

1. Studies, using a wide variety of stressors, have clearly indicated that the pattern of neuroendocrine response is dependent upon the stress stimulus applied. 2. The Tyr-MIF-1 family of peptides (Tyr-MIF-1s) includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1. These neuropeptides, neuromodulators are able to inhibit the expression of some forms of stress-induced analgesia. 3. The aim of this study was to compare changes in ACTH and corticosterone (CORT) concentration after various stressors (immobilization, cold and heat), as well as after injection of investigated Tyr-MIF-1s peptides. 4. According to our results, hypothalamic-pituitary-adrenal (HPA) system was activated by all the stressors applied. Heat and immobilization are stronger stressors, as the exposure of animals to a high ambient temperature and immobilization resulted in the highest rise of plasma ACTH and CORT concentration when compared with cold stress. Moreover, all the investigated peptides from Tyr-MIF-1 family, administered after application of stressors, inhibited the elevations in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) plasma concentrations significantly. 5. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release. We suggest that Tyr-MIF-1 peptides may possess anti-stressor effects, as they inhibited stress-induced rising in two hormones that were investigated.

An unusual case of ectopic ACTH syndrome.

PubMed

Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C

2012-02-01

Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Obtaining growth hormone from calf blood

NASA Technical Reports Server (NTRS)

Kalchev, L. A.; Ralchev, K. K.; Nikolov, I. T.

1979-01-01

The preparation of a growth hormone from human serum was used for the isolation of the hormone from calf serum. The preparation was biologically active - it increased the quantity of the free fatty acids released in rat plasma by 36.4 percent. Electrophoresis in Veronal buffer, ph 8.6, showed the presence of a single fraction having mobility intermediate between that of alpha and beta globulins. Gel filtration through Sephadex G 100 showed an elutriation curve identical to that obtained by the growth hormone prepared from pituitary glands.

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency.

PubMed

Toublanc, J E; Couprie, C; Garnier, P; Job, J C

1989-06-01

The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below -2 SD in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1-2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release.

PubMed

Gisquet-Verrier, Pascale; Botreau, Fanny; Venero, Cesar; Sandi, Carmen

2004-05-01

Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes.

Reduced nocturnal ACTH-driven cortisol secretion during critical illness

PubMed Central

Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.

2014-01-01

Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590

Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

NASA Technical Reports Server (NTRS)

Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

1999-01-01

Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

ACTH has beneficial effects on stuttering in ADHD and ASD patients with ESES: A retrospective study.

PubMed

Altunel, Attila; Sever, Ali; Altunel, Emine Özlem

2017-02-01

Etiology of stuttering remains unknown and no pharmacologic intervention has been approved for treatment. We aimed to evaluate EEG parameters and the effect of adrenocorticotropic hormone (ACTH) therapy in stuttering. In this retrospective study, 25 patients with attention deficit and hyperactivity (ADHD) or autism spectrum disorder (ASD), and comorbid stuttering were followed and treated with ACTH for electrical status epilepticus in sleep (ESES). Sleep EEGs were recorded at referral and follow-up visits and short courses of ACTH were administered when spike-wave index (SWI) was ⩾15%. The assessment of treatment effectiveness was based on reduction in SWI, and the clinician-reported improvement in stuttering, and ADHD or ASD. Statistical analyses were conducted in order to investigate the relationship between the clinical and EEG parameters. Following treatment with ACTH, a reduction in SWI in all the patients was accompanied by a 72% improvement in ADHD or ASD, and 83.8% improvement in stuttering. Twelve of the 25 patients with stuttering showed complete treatment response. Linear regressions established that SWI at final visit significantly predicted improvement in ADHD or ASD, and in stuttering. If symptoms had recurred, improvement was once again achieved with repeated ACTH therapies. Stuttering always improved prior to, and recurred following ADHD or ASD. The underlying etiology leading to ESES may play a significant role in the pathophysiology of stuttering and connect stuttering to other developmental disorders. ACTH therapy has beneficial effects on stuttering and improves EEG parameters. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers.

PubMed

Alía, P; Villabona, C; Giménez, O; Sospedra, E; Soler, J; Navarro, M A

2006-09-01

No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.

21 CFR 862.1370 - Human growth hormone test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

21 CFR 862.1370 - Human growth hormone test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

The Calcium-Sensing Receptor Couples to Gαs and Regulates PTHrP and ACTH Secretion in Pituitary Cells

PubMed Central

Mamillapalli, Ramanaiah; Wysolmerski, John

2013-01-01

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor (GPCR) that binds and signals in response to extracellular calcium and other polycations. It is highly expressed on parathyroid and kidney cells, where it participates in the regulation of systemic calcium homeostasis. It is also expressed on many other cell types and is involved in a wide array of biological functions such as cell growth and differentiation, ion transport and hormone secretion. It has been described to couple to several different G-proteins including Gαi/0, Gαq/11 and Gα12/13. Recently, it has also been shown to stimulate cAMP production by coupling to Gαs in immortalized or malignant breast cells. The CaR is expressed on cells in the anterior pituitary and had previously been described to stimulate cAMP production in these cells. In this report, we examined signaling from the CaR in murine pituitary corticotroph-derived, AtT-20 cells. We found that CaR activation led to the stimulation of cAMP production, and PTHrP and ACTH secretion from these cells. Furthermore, manipulation of cAMP levels was able to modulate PTHrP and ACTH secretion independent of changes in extracellular calcium. Finally, we demonstrated that the CaR couples to Gαs in AtT-20 cells. Therefore, in pituitary corticotroph-like cells, as in breast cancer cells, the CaR utilizes Gαs and activates cAMP production to stimulate hormone secretion. PMID:20032198

The effects of physical therapeutic agents on serum levels of stress hormones in patients with osteoarthritis

PubMed Central

Tönük, Şükrü Burak; Serin, Erdinc; Ayhan, Fikriye Figen; Yorgancioglu, Zeynep Rezan

2016-01-01

Abstract To investigate the effects of physical agents on the levels of stress hormones in patients with osteoarthritis (OA). Transcutaneous electrical nerve stimulation, hot packs, and therapeutic ultrasound were applied to the lumbar region and knees of patients with OA. Blood samples were taken for the measurement of the serum levels of glucose, insulin (INS), growth hormone (GH), prolactin (PRL), cortisol (COR), and plasma adrenocorticotropic hormone (ACTH) immediately before and after the 1st session, to investigate the acute effects of those physical agents on the endocrine system. The hormone levels were also measured every 5 sessions in a total of 10 sessions. The treatment response was also evaluated by using the visual analogue scale (VAS), Roland Morris Disability Questionnaire (RMDQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) throughout the therapy period. After the 1st session, there was a decrease in INS levels and a mild decrease in PRL levels (P = 0.001 and P < 0.05, respectively). Throughout the 10-session therapy period, the INS levels increased, whereas the ACTH and COR levels decreased (P < 0.05 for all). The VAS-spine, RMDQ, VAS-knee, and WOMAC scores decreased (P = 0.001 for VAS-spine and P < 0.001 for all others). A positive correlation was detected between the changes in serum COR and WOMAC-pain score (P < 0.05). Although the combination therapy caused changes in INS level accompanied with steady glucose levels, the application of physical agents did not adversely affect the hormone levels. The decrease in ACTH and COR levels may be attributed to the analgesic effect of agents and may be an indicator of patient comfort through a central action. PMID:27583888

Growth hormone stimulation test (image)

MedlinePlus

... test is performed by administering the amino acid arginine in a vein to raise hGH levels. The ... to secrete growth hormone in response to the arginine. Lack of hGH can cause growth retardation in ...

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

PubMed

Erfe, J Mark; Perry, Avital; McClaskey, John; Inzucchi, Silvio E; James, Whitney Sheen; Eid, Tore; Bronen, Richard A; Mahajan, Amit; Huttner, Anita; Santos, Florecita; Spencer, Dennis

2017-10-13

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient

Growth Hormone Therapy in Adults with Prader-Willi Syndrome.

PubMed

Vogt, Karen S; Emerick, Jill E

2015-04-16

Prader-Willi syndrome (PWS) is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

PubMed

Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

Diagnosis of growth hormone deficiency in the paediatric and transitional age.

PubMed

Chinoy, A; Murray, P G

2016-12-01

Growth hormone deficiency is a rare cause of childhood short stature, but one for which treatment exists in the form of recombinant human growth hormone. A diagnosis of growth hormone deficiency is made based on auxology, biochemistry and imaging. Although no diagnostic gold standard exists, growth hormone provocation tests are considered the mainstay of diagnostic investigations. However, these must be interpreted with caution in view of issues with variability and reproducibility, as well as the limited evidence-base for cut-off values used to distinguish growth hormone deficient and non-growth hormone deficient subjects. In addition, nutritional and pubertal status can affect results, with no consensus on the role of priming with sex steroid hormones. Difficulties with assays exist both for growth hormone as well as insulin-like growth factor-1. Pituitary magnetic resonance imaging is a useful diagnostic, and possibly prognostic, aid. Although genetic testing is not routine, the discovery of more relevant mutations makes it an increasingly important investigation. Children with growth hormone deficiency are retested biochemically on completion of growth, to assess whether they remain so into adulthood. Copyright © 2016. Published by Elsevier Ltd.

Familial isolated growth-hormone deficiency with advanced sexual maturation.

PubMed

Kauschansky, A; Cohen, H A; Varsano, I; Laron, Z; Frydman, M

1993-02-01

Two brothers, aged 15 1/2 and 13 1/2 years, with dwarfism, microcephaly, and advanced sexual and skeletal maturation are described. One patient was mentally retarded. The parents were first cousins. Endocrine studies of these patients documented low growth-hormone levels after clonidine and insulin stimulation and blunted growth-hormone response to growth hormone releasing hormone. Gonadotropin releasing hormone stimulation produced no changes in levels of luteinizing and follicle-stimulating hormones. Basal levels of 17-alpha-hydroxyprogesterone were elevated in the two patients and increased further in response to stimulation with corticotropin. Levels of testosterone, dehydroepiandrosterone sulfate, and androstenedione were variably increased in both patients and showed a proportional increase on stimulation with human chorionic gonadotropin. To our knowledge, this is the first report of a familial association between growth-hormone deficiency and advanced bone and sexual maturation. A pituitary and an independent adrenal defect could account for the observations in these patients, but in view of the familial recurrence, a common underlying defect is possible.

Treatment with Growth Hormone for Adults with Growth Hormone Deficiency Syndrome: Benefits and Risks

PubMed Central

Díez, Juan J.; Sangiao-Alvarellos, Susana; Cordido, Fernando

2018-01-01

Pharmacological treatment of growth hormone deficiency (GHD) in adults began in clinical practice more than 20 years ago. Since then, a great volume of experience has been accumulated on its effects on the symptoms and biochemical alterations that characterize this hormonal deficiency. The effects on body composition, muscle mass and strength, exercise capacity, glucose and lipid profile, bone metabolism, and quality of life have been fully demonstrated. The advance of knowledge has also taken place in the biological and molecular aspects of the action of this hormone in patients who have completed longitudinal growth. In recent years, several epidemiological studies have reported interesting information about the long-term effects of GH replacement therapy in regard to the possible induction of neoplasms and the potential development of diabetes. In addition, GH hormone receptor polymorphism could potentially influence GH therapy. Long-acting GH are under development to create a more convenient GH dosing profile, while retaining the excellent safety, efficacy, and tolerability of daily GH. In this article we compile the most recent data of GH replacement therapy in adults, as well as the molecular aspects that may condition a different sensitivity to this treatment. PMID:29562611

Hydrocortisone and ACTH levels in manned spaceflight

NASA Technical Reports Server (NTRS)

Leach, C. S.; Campbell, B. O.

1974-01-01

The plasma hydrocortisone, plasma ACTH, and urinary hydrocortisone values were recorded for each man of the crews of Apollo flights eight through fifteen, 30, 14, and 5 days before flight, immediately after spaceflight recovery, and on future days until the return of most variables to preflight values. The plasma and urinary preflight hydrocortisone values were significantly higher than the postflight values. This result is discussed in terms of three possible explanations: (1) the adrenal-cortical function is suppressed during spaceflight; (2) the activity in flight may amount to stressful exercise, which tests have shown can cause a decrease in plasma adrenocortical hormones; and (3) the in-flight work-rest cycles may be such as to affect the circadian periodicity of the pituitary-adrenal function.

Growth hormone regulation of follicular growth.

PubMed

Lucy, Matthew C

2011-01-01

The somatotropic axis-consisting of growth hormone (GH), the insulin-like growth factors 1 and 2 (IGF1 and IGF2), GH binding protein (GHBP), IGF binding proteins (IGFBPs) 1 to 6, and the cell-surface receptors for GH and the IGFs-has major effects on growth, lactation and reproduction. The primary target tissues for GH are involved in growth and metabolism. The functionality of the somatotropic axis depends in part on the expression of liver GH receptor (GHR), which determines the amount of IGF1 released from the liver in response to GH. The IGF1 acts as a pleiotropic growth factor and also serves as the endocrine negative feedback signal controlling pituitary GH secretion. Growth hormone and IGF1 undergo dynamic changes throughout the life cycle, particularly when animals are either growing, early post partum or lactating. Cells within the reproductive tract can respond directly to GH but to a lesser degree than the primary target tissues. The major impact that GH has on reproduction, therefore, may be secondary to its systemic effects on metabolism (including insulin sensitivity) or secondary to the capacity for GH to control IGF1 secretion. Insulin-like growth factor 1 and IGFBP are also synthesised within the ovary and this local synthesis is a component of the collective IGF1 action on the follicle. Future studies of GH should focus on its direct effects on the follicle as well as its indirect effects mediated by shifts in nutrient metabolism, insulin sensitivity, IGF1 and IGFBP.

Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

ERIC Educational Resources Information Center

Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

Growth arrest despite growth hormone replacement, post-craniopharyngioma surgery.

PubMed Central

DeVile, C J; Hayward, R D; Neville, B G; Grant, D B; Stanhope, R

1995-01-01

Children with growth failure, whether secondary to an endocrinopathy such as growth hormone deficiency or secondary to neurological handicap with poor nutrient intake, grow at a subnormal rate but it is most unusual for a child to have complete growth arrest. PMID:7745571

Psychomotor retardation in a girl with complete growth hormone deficiency.

PubMed

Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

2013-01-01

Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment

PubMed Central

Butler, Merlin G.; Lee, Jaehoon; Cox, Devin M.; Manzardo, Ann M.; Gold, June-Anne; Miller, Jennifer L.; Roof, Elizabeth; Dykens, Elisabeth; Kimonis, Virginia; Driscoll, Daniel J.

2018-01-01

The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone–treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non–growth hormone–treated PWS individuals. Growth chart implications and recommended usage are discussed. PMID:26842920

Growth hormone treatment for growth hormone deficiency and idiopathic short stature: new guidelines shaped by the presence and absence of evidence.

PubMed

Grimberg, Adda; Allen, David B

2017-08-01

The Pediatric Endocrine Society recently published new guidelines for the use of human growth hormone (hGH) and human insulin-like growth factor-I (hIGF-I) treatment for growth hormone deficiency, idiopathic short stature, and primary IGF-I deficiency in children and adolescents. This review places the new guidelines in historical contexts of the life cycle of hGH and the evolution of US health care, and highlights their future implications. The new hGH guidelines, the first to be created by the Grading of Recommendations Assessment, Development and Evaluation approach, are more conservative than their predecessors. They follow an extended period of hGH therapeutic expansion at a time when US health care is pivoting toward value-based practice. There are strong supporting evidence and general agreement regarding the restoration of hormonal normalcy in children with severe deficiency of growth hormone or hIGF-I. More complex are issues related to hGH treatment to increase growth rates and heights of otherwise healthy short children with either idiopathic short stature or 'partial' isolated idiopathic growth hormone deficiency. The guidelines-developing process revealed fundamental questions about hGH treatment that still need evidence-based answers. Unless and until such research is performed, a more restrained hGH-prescribing approach is appropriate.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

PubMed

Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

2015-08-01

Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

PubMed

Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

2015-01-01

Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

PubMed

Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O

2000-09-28

Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

Genetics of Isolated Growth Hormone Deficiency

PubMed Central

2010-01-01

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required, and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency (GHD). Because Insulin−like Growth Factor−I (IGF−I) plays a pivotal role, GHD could also be considered as a form of IGF−I deficiency (IGFD). Although IGFD can develop at any level of the GH−releasing hormone (GHRH)−GH−IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency, they may present initially as GHD. Conflict of interest:None declared. PMID:21274339

Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

NASA Technical Reports Server (NTRS)

Brooks, V. L.; Keil, L. C.

1992-01-01

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

IGF-1 and insulin as growth hormones.

PubMed

Laron, Zvi

2004-01-01

IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

[The effect of a single inhalation of mineral water on the blood hormonal status in healthy volunteers].

PubMed

Khinchagov, B P; Polushina, N D; Frolkov, V K

1998-01-01

Concentrations of ACTH, TTH, STH, LH, PSH, hydrocortisone, insulin, glucagone, triiodthyronine, thyroxine, aldosterone, glucose and unesterified fatty acids (NEFA) were measured in the blood of 23 healthy male volunteers aged 18 to 35 years 15, 30 and 60 min after a single nose inhalation and oral intake of mineral water Essentuki No. 17. Inhalation of Essentuki No. 17 stimulated secretion of the hormones and some parameters of metabolic reactions: the levels of glucose, NEFA, hydrocortisone, aldosterone, TTH, PSH and LH rose while those of insulin and growth hormone decreased. Oral intake of this water brought about the same changes in the hormone status except blood insulin the levels of which went up.

ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1981-01-01

The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

Growth hormone response to feeding in term and preterm neonates.

PubMed

Adrian, T E; Lucas, A; Bloom, S R; Aynsley-Green, A

1983-03-01

Plasma growth hormone concentrations were measured in 248 healthy term and preterm infants. At birth growth hormone concentrations in cord blood from both term and preterm babies were approximately 100-fold higher than those in blood drawn from healthy adults. By the sixth postnatal day basal pre-feed levels had fallen in term neonates by 65% and a marked postprandial rise was apparent; preterm infants did not show this initial fall in preprandial hormone levels nor was any response to feeding seen. However a fall in preprandial concentrations accompanied by the development of postprandial surges in growth hormone occurred during the next 2 weeks so that by 24 days the postprandial rise was similar to that of term neonates on the sixth day. We conclude that although the initial postnatal changes in plasma growth hormone concentrations are different in preterm and term infants, feeding is a major stimulus to growth hormone secretion in both groups of neonates. Further work is needed to define the precise role of this hormone in neonatal metabolic adaptation.

Effect of growth hormone deficiency on brain structure, motor function and cognition.

PubMed

Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and

Stimulation of growth hormone secretion from seabream pituitary cells in primary culture by growth hormone secretagogues is independent of growth hormone transcription.

PubMed

Chan, C B; Fung, C K; Fung, Wendy; Tse, Margaret C L; Cheng, Christopher H K

2004-10-01

The action of a number of growth hormone secretagogues (GHS) on growth hormone (GH) secretion and gene expression was studied in a primary culture of pituitary cells isolated from the black seabream Acanthopagrus schlegeli. The peptide GHS employed included growth hormone-releasing peptide (GHRP)-2, ipamorelin, and human ghrelin. The nonpeptide GHS employed included the benzolactam GHS L692,585 and the spiropiperidine GHS L163,540. Secreted GH was measured in the culture medium by an enzyme-linked immunosorbent assay (ELISA) method using a specific antibody against seabream GH. The GH mRNA content in the incubated cells was assessed by reverse transcription polymerase chain reaction (RT-PCR) using a pair of gene-specific primers designed from the cloned black seabream GH cDNA sequence. A dose-dependent stimulation of GH release was demonstrated by all the GHS tested, except human ghrelin, with EC(50) values in the nanomolar range. Simultaneous measurement of GH mRNA levels in the incubated seabream pituitary cells indicated that the GHS-stimulated increase in GH secretion was not paralleled by corresponding changes in GH gene expression. In contrast to the situation previously reported in the rat, no change in GH gene expression was noticed in the seabream pituitary cells even though the time of stimulation by GHS was increased up to 48 h, confirming that the GHS-stimulated GH secretion in seabream is independent of GH gene transcription.

Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations.

PubMed

Martari, Marco; Salvatori, Roberto

2009-01-01

The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptors family. It is expressed almost exclusively in the anterior pituitary, where it is necessary for somatotroph cells proliferation and for GH synthesis and secretion. Mutations in the human GHRHR gene (GHRHR) can impair ligand binding and signal transduction, and have been estimated to cause about 10% of autosomal recessive familial isolated growth hormone deficiency (IGHD). Mutations reported to date include five splice donor site mutations, two microdeletions, two nonsense mutations, seven missense mutations, and one mutation in the promoter. These mutations have an autosomal recessive mode of inheritance, and heterozygous individuals do not show signs of IGHD, although the presence of an intermediate phenotype has been hypothesized. Conversely, patients with biallelic mutations have low serum insulin-like growth factor-1 and GH levels (with absent or reduced GH response to exogenous stimuli), resulting--if not treated--in proportionate dwarfism. This chapter reviews the biology of the GHRHR, the mutations that affect its gene and their effects in homozygous and heterozygous individuals. Copyright © 2009 Elsevier Inc. All rights reserved.

ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE ACTH ANDCORTICOSTERONE RELEASE AND CAUSE CONDITIONED TASTE AVERSION.

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) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...

Growth hormone secretion in Turner's syndrome and influence of oxandrolone and ethinyl oestradiol.

PubMed

Massarano, A A; Brook, C G; Hindmarsh, P C; Pringle, P J; Teale, J D; Stanhope, R; Preece, M A

1989-04-01

We investigated 24 hour growth hormone secretion by intermittent 20 minute blood sampling in 34 prepubertal patients with Turner's syndrome, aged 4.3-12.4 years. Growth hormone profiles were analysed by the PULSAR programme and results expressed as the sum of growth hormone pulse amplitudes. Six patients had abnormal growth hormone pulse frequencies. In the remaining 28, growth hormone pulse amplitudes declined significantly with increasing age, but there was no correlation between growth hormone pulse amplitudes and growth rates. Concentrations of insulin like growth factor-1 (IGF-1) rose with age but did not correlate with either growth rates or growth hormone secretion. Fifteen patients were given oxandrolone and 11 low dose ethinyl oestradiol. Both agents increased height velocity without increasing growth hormone secretion. We conclude that the relation between growth hormone secretion and growth in Turner's syndrome is less certain than in normal children. End organ resistance is probably due to a skeletal dysplasia. Both oxandrolone and low dose ethinyl oestradiol improve the growth of girls with Turner's syndrome, but their mechanism of action remains uncertain.

Growth hormone positive effects on craniofacial complex in Turner syndrome.

PubMed

Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

2016-11-01

Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

The History of Growth Hormone Treatment for GHD in Japan.

PubMed

Yokoya, Susumu; Tanaka, Toshiaki

2017-03-01

In Japan, treatment of growth hormone deficiency with pituitary-extracted human growth hormone (phGH) was covered by health insurance for the first time in 1975. However, because of the shortage of phGH, the Foundation for Growth Science (FGS) was founded in 1977 to control the use of the product by its registration system and to collect pituitary glands in Japan. In 1986, recombinant human growth hormone was first approved. Since then, the FGS has been involved in the harmonization of growth hormone measurement, assessment for treatment eligibility according to the diagnostic criteria by the research group of the Ministry of Health and Welfare, and database generation and its utilization. Copyright© of YS Medical Media ltd.

Pneumocystis Pneumonia Concomitant with Ectopic ACTH Syndrome Caused by a Large Cell Neuroendocrine Carcinoma of the Thymus.

PubMed

Oda, Naohiro; Miyahara, Nobuaki; Tabata, Masahiro; Minami, Daisuke; Ninomiya, Kiichiro; Kanehiro, Arihiko; Komatsubara, Motoshi; Inagaki, Kenichi; Tanimoto, Mitsune; Kiura, Katsuyuki

2017-01-01

We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.

Recombinant Bovine Growth Hormone Criticism Grows.

ERIC Educational Resources Information Center

Gaard, Greta

1995-01-01

Discusses concerns related to the use of recombinant bovine growth hormone in the United States and other countries. Analyses the issue from the perspectives of animal rights, human health, world hunger, concerns of small and organic farmers, costs to the taxpayer, and environmental questions. A sidebar discusses Canadian review of the hormone.…

Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.

PubMed

Kuenzel, Heike E; Steiger, Axel; Held, Katja; Antonijevic, Irina A; Frieboes, Ralf-Michael; Murck, Harald

2005-07-01

Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia. CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs. Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night. After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night. While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

PubMed Central

Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J

2016-01-01

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257

Growth charts for non-growth hormone treated Prader-Willi syndrome.

PubMed

Butler, Merlin G; Lee, Jaehoon; Manzardo, Ann M; Gold, June-Anne; Miller, Jennifer L; Kimonis, Virginia; Driscoll, Daniel J

2015-01-01

The goal of this study was to generate and report standardized growth curves for weight, height, head circumference, and BMI for non-growth hormone-treated white male and female US subjects with Prader-Willi syndrome (PWS) between 3 and 18 years of age and develop standardized growth charts. Anthropometric measures (N = 133) were obtained according to standard methods from 120 non-growth hormone-treated white subjects (63 males and 57 females) with PWS between 3 and 18 years of age. Standardized growth curves were developed for the third, 10th, 25th, 50th, 75th, 90th, and 97th percentiles by using the LMS method for weight, height, head circumference, and BMI for PWS subjects along with the normative third, 50th, and 97th percentiles from national and international growth data. The LMS smoothing procedure summarized the distribution of the anthropometric variables at each age using three parameters: power of the Box-Cox transformation λ (L), median μ (M) and coefficient of variation δ (S). Weight, height, head circumference, and BMI standardized growth charts representing 7 percentile ranges were developed from 120 non-growth hormone-treated white male and female US subjects with PWS (age range: 3-18 years) and normative third, 50th, and 97th percentiles from national and international data. We encourage the use of syndrome-specific growth standards to examine and evaluate subjects with PWS when monitoring growth patterns and determining nutritional and obesity status. These variables can be influenced by culture, individual medical care, diet intervention, and physical activity plans. Copyright © 2015 by the American Academy of Pediatrics.

Neuroprotective Actions of Ghrelin and Growth Hormone Secretagogues

PubMed Central

Frago, Laura M.; Baquedano, Eva; Argente, Jesús; Chowen, Julie A.

2011-01-01

The brain incorporates and coordinates information based on the hormonal environment, receiving information from peripheral tissues through the circulation. Although it was initially thought that hormones only acted on the hypothalamus to perform endocrine functions, it is now known that they in fact exert diverse actions on many different brain regions including the hypothalamus. Ghrelin is a gastric hormone that stimulates growth hormone secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, growth hormone secretagogues–GH secretagogue-receptor, which is most highly expressed in the pituitary and hypothalamus. In addition, ghrelin has effects on learning and memory, reward and motivation, anxiety, and depression, and could be a potential therapeutic agent in neurodegenerative disorders where excitotoxic neuronal cell death and inflammatory processes are involved. PMID:21994488

Modified Clonidine Testing for Growth Hormone Stimulation Reveals α2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency.

PubMed

Willaschek, Christian; Meint, Sebastian; Rager, Klaus; Buchhorn, Reiner

2015-01-01

The association between short stature and increased risk of ischemic heart disease has been subject to studies for decades. The recent discussion of cardiovascular risk during growth hormone therapy has given new importance to this question. We have hypothesized that the autonomic system is a crucial element relating to this subject. Heart rate variability calculated from 24-hour electrocardiogram data is providing insight into the regulatory state of the autonomous nervous system and is an approved surrogate parameter for estimating cardiovascular risk. We have calculated heart rate variability during clonidine testing for growth hormone stimulation of 56 children. As clonidine is a well-known effector of the autonomous system, stimulating vagal tone and decreasing sympathetic activity, we compared the autonomous reactions of children with constitutional growth delay (CGD), growth hormone deficiency (GHD) and former small for gestational age (SGA). During clonidine testing children with CGD showed the expected α2-adrenoreceptor mediated autonomous response of vagal stimulation for several hours. This vagal reaction was significantly reduced in the SGA group and nearly non- existent in the GHD group. Children with GHD show a reduced autonomous response to clonidine indicating α2-adrenoreceptor sub sensitivity. This can be found prior to the start of growth hormone treatment. Since reduction of HRV is an approved surrogate parameter, increased cardiovascular risk has to be assumed for patients with GHD. In the SGA group a similar but less severe reduction of the autonomous response to clonidine was found. These findings may enrich the interpretation of the data on growth hormone therapy, which are being collected by the SAGhE study group.

Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure

PubMed Central

Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

2015-01-01

Objectives In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. Methods This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. Results Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. Conclusion This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula. PMID:26622960

Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure.

PubMed

Kucuk, Nurten; Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

2015-12-01

In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula.

Hormones, Nicotine and Cocaine: Clinical Studies

PubMed Central

Mello, Nancy K.

2009-01-01

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (< 20 min), ratings of “High” and “Rush” began to decrease within one or two puffs of a high nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

Treatment of idiopathic FSGS with adrenocorticotropic hormone gel.

PubMed

Hogan, Jonathan; Bomback, Andrew S; Mehta, Kshama; Canetta, Pietro A; Rao, Maya K; Appel, Gerald B; Radhakrishnan, Jai; Lafayette, Richard A

2013-12-01

Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

Cushing's syndrome due to ectopic production of corticotropin-releasing hormone in an infant with ganglioneuroblastoma.

PubMed

Zangeneh, Farhad; Young, William F; Lloyd, Ricardo V; Chiang, Myra; Kurczynski, Elizabeth; Zangeneh, Fereydoun

2003-01-01

To report the first recognized case of Cushing's syndrome due to a corticotropin-releasing hormone (CRH)-secreting ganglioneuroblastoma, which was found in an 18-month-old boy with hypertensive encephalopathy. The clinical, biochemical, and immunohistochemical characteristics of this rare syndrome are described, and the relevant literature is reviewed. An 18-month-old boy with a history of recent weight gain was admitted because of sudden onset of right fixed esotropia and left facial palsy after episodes of emesis. Magnetic resonance imaging showed old left frontal lobe and right hypothalamic infarcts. The patient had generalized obesity, decelerated linear growth, hypertrichosis, hypertension (144/103 mm Hg), hypokalemia, and proteinuria. The 24-hour urinary excretion of free cortisol, catecholamines, and metanephrines was increased. The serum cortisol concentration after a 1-mg overnight dexamethasone suppression test (DST) was 53.7 mg/dL (normal, <5). The serum adrenocorticotropic hormone (ACTH) concentration was 7 pg/mL (normal, 10 to 60), and the CRH level was 439 pg/mL (normal, 24 to 40). An overnight high-dose DST (8 mg) failed to suppress serum cortisol; however, both cortisol and ACTH were responsive to ovine CRH stimulation. Despite discordant dynamic endocrine testing and negative somatostatin receptor scintigraphy, computed tomography showed a right 3.6- by 3.0-cm extra-adrenal retroperitoneal mass with central calcification extending 7 cm cephalocaudally. The patient underwent exploratory laparotomy, followed by chemotherapy. Findings on light microscopic and immunohistochemical examination of the retroperitoneal mass were consistent with a ganglioneuroblastoma that expressed CRH, pro-opiomelanocortin, and ACTH. The evaluation of Cushing's syndrome is one of the most complex endocrine challenges. In this case, it was due to ectopic production of CRH by a ganglioneuroblastoma. Because most CRH-producing tumors also secrete ACTH, the ectopic production

Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

USDA-ARS?s Scientific Manuscript database

Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

Prolactin and growth hormone in fish osmoregulation

USGS Publications Warehouse

Sakamoto, T.; McCormick, S.D.

2006-01-01

Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids. ?? 2005 Elsevier Inc. All rights reserved.

Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure.

PubMed

Gunasekaran, N; Long, L E; Dawson, B L; Hansen, G H; Richardson, D P; Li, K M; Arnold, J C; McGregor, I S

2009-11-01

Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg.kg(-1)) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.

Debate: idiopathic short stature should be treated with growth hormone.

PubMed

Ambler, Geoffrey R; Fairchild, Jan; Wilkinson, Dominic J C

2013-03-01

In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with 'idiopathic' short stature are not 'short, normal children' and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost-effective in idiopathic short-stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Growth hormone deficiency: an unusual presentation of floating harbor syndrome.

PubMed

Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos

2011-01-01

Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.

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.

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test.

PubMed

Ritzel, Katrin; Beuschlein, Felix; Berr, Christina; Osswald, Andrea; Reisch, Nicole; Bidlingmaier, Martin; Schneider, Harald; Honegger, Jürgen; Geyer, Lucas L; Schopohl, Jochen; Reincke, Martin

2015-08-01

The aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome. We retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B) after 8 mg of dexamethasone was evaluated as a supplementary criterion. An increase in ACTH of ≥ 43%B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases. The present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive. © 2015 European Society of Endocrinology.

Hormonal regulation of wheat growth during hydroponic culture

NASA Technical Reports Server (NTRS)

Wetherell, Donald

1988-01-01

Hormonal control of root growth has been explored as one means to alleviate the crowding of plant root systems experienced in prototype hydroponic biomass production chambers being developed by the CELSS Breadboard Project. Four plant hormones, or their chemical analogs, which have been reported to selectively inhibit root growth, were tested by adding them to the nutrient solutions on day 10 of a 25 day growth test using spring wheat in hydroponic cultures. Growth and morphological changes is both shoot and root systems were evaluated. In no case was it possible to inhibit root growth without a comparable inhibition of shoot growth. It was concluded that this approach is unlikely to prove useful for wheat.

Response to growth hormone therapy in adolescents with familial panhypopituitarism.

PubMed

Kulshreshtha, B; Eunice, M; Ammini, A C

2010-04-01

Familial combined pituitary hormone deficiency is a rare endocrine disorder. We describe growth patterns of four children (3 females and 1 male) from two families with combined pituitary hormone deficiency. These children received growth hormone at ages ranging from 14.5 years to 19 years. While all the female siblings reached their target height, the male sibling was much shorter than mid parental height. The reasons for sexual dimorphism in growth patterns in these children are unclear.

[TREATMENT OF SHORT STATURE PATIENTS WITH NOPMAL GROWTH HORMONE SECRETION OF HYPOPHIS].

PubMed

Sprinchuk, N A; Samson, O J; Bol'shova, E V

2014-12-01

The article presents the treatment outcome in 86 children with short stature associated with different endocrine pathology and saved growth hormone secretion (congenital adrenal hyperplasia chondrodystrophy, Turner syndrome, idiopathic short stature, syndrome biologically inactive growth hormone and other genetically determined pathology). This study extends prior knowledge about the outcomes of the treatment with recombinant growth hormone and luteinizing hormone--releasing hormone analogue (alone or in combination) in short patients with poor prognosis of final height.

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

PubMed

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report

PubMed Central

2011-01-01

Introduction Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. Case presentation We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. Conclusion The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily

Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report.

PubMed

Cotta, Oana R; Santarpia, Libero; Curtò, Lorenzo; Aimaretti, Gianluca; Corneli, Ginevra; Trimarchi, Francesco; Cannavò, Salvatore

2011-07-11

Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth

Effects of fasting on growth hormone, growth hormone receptor, and insulin-like growth factor-I axis in seawater-acclimated tilapia, Oreochromis mossambicus.

PubMed

Fox, B K; Riley, L G; Hirano, T; Grau, E G

2006-09-15

Effects of fasting on the growth hormone (GH)--growth hormone receptor (GHR)-insulin-like growth factor-I (IGF-I) axis were characterized in seawater-acclimated tilapia (Oreochromis mossambicus). Fasting for 4 weeks resulted in significant reductions in body weight and specific growth rate. Plasma GH and pituitary GH mRNA levels were significantly elevated in fasted fish, whereas significant reductions were observed in plasma IGF-I and hepatic IGF-I mRNA levels. There was a significant negative correlation between plasma levels of GH and IGF-I in the fasted fish. No effect of fasting was observed on hepatic GHR mRNA levels. Plasma glucose levels were reduced significantly in fasted fish. The fact that fasting elicited increases in GH and decreases in IGF-I production without affecting GHR expression indicates a possible development of GH resistance.

Growth Hormone: Use and Abuse

MedlinePlus

... is used to treat • Growth hormone deficiency • Muscle wasting (loss of muscle tissue) from HIV • Short bowel ... and strength, with increased muscle and decreased fat mass. But other studies did not show similar benefits. ...

Polycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.

PubMed

Urdl, W

1988-01-01

Thirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH

Plurihormonal pituitary adenoma immunoreactive for thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, and prolactin.

PubMed

Luk, Cynthia T; Kovacs, Kalman; Rotondo, Fabio; Horvath, Eva; Cusimano, Michael; Booth, Gillian L

2012-01-01

To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment. A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved. Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.

[Behavior of circadian rhythm of ACTH and cortisol in 16 normal subjects after a balanced normocaloric diet and after a high protein diet (Cosinor mean method)].

PubMed

Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P

1983-01-31

In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.

Hormonal responses of metoclopramide-treated subjects experiencing nausea or emesis during parabolic flight

NASA Technical Reports Server (NTRS)

Kohl, Randall L.

1987-01-01

The concentrations of adrenocorticotropic hormone (ACTH), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) in 22 subjects administered 10 to 20 mg of metoclopramide prior to parabolic flight are measured. The effect of metoclopramide on motion sickness is examined. It is observed that metoclopramide is ineffective in the modulation of motion sickness due to stressful linear and angular acceleration and orbital flight, and it does not affect serum hormones prior to parabolic flight. It is detected that the serum level of AVP declines following emesis induced by parabolic flight and stressful angular acceleration; the serum levels of ACTH and EPI are elevated by parabolic flight and stressful angular acceleration; and serum NE is significantly elevated immediately following emesis. The possible roles of these hormones in the etiology of space motion sickness are discussed.

Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

PubMed

Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

2018-04-01

Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets.

PubMed

Povedano, S T; Pastor, C V; Seoane, C P; Reina, L J; Moreno, M A; Ortega, R P; López-Rubio, F; López, P B

2001-06-01

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

PubMed

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-11-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children

PubMed Central

De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

2016-01-01

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene–environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene–environment interactions in children treated with r-hGH. PMID:26503811

Gradual Loss of ACTH Due to a Novel Mutation in LHX4: Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism

PubMed Central

Takagi, Masaki; Ishii, Tomohiro; Inokuchi, Mikako; Amano, Naoko; Narumi, Satoshi; Asakura, Yumi; Muroya, Koji; Hasegawa, Yukihiro; Adachi, Masanori; Hasegawa, Tomonobu

2012-01-01

Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations. This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic–pituitary -adrenal function is recommended for CH patients with LHX4 mutations. PMID:23029363

Growth Hormone Deficiency in Children

MedlinePlus

... or the brain, and can rule out a brain tumor. Did you know? Most children with growth hormone deficiency grow less than two inches (5 centimeters) each year. How is a child with GHD treated? Children with GHD receive treatment ...

Growth hormone investigation in patients with mental dysfunction.

PubMed

Pozsonyi, J; Friesen, H

1971-01-09

Seventy-three children with disorders of physical growth and mental development were stimulated by insulin hypoglycemia and arginine infusion and their human growth hormone (HGH) responses were determined. Only four patients exhibited absent or impaired pituitary hormone secretion and one of them presented a unique syndrome of panhypopituitarism associated with intrauterine growth retardation, long eyelashes and eyebrows, sparse hair and degeneration of the retina. Statistical analysis indicated no significant HGH peak concentrations in groups of either tall males or stunted females who possessed various sex chromosome abnormalities, nor did these groups differ in a variety of clinical parameters including age, physical growth, birth weight and intelligence.

Growth Hormone Investigation in Patients with Mental Dysfunction

PubMed Central

Pozsonyi, J.; Friesen, H.

1971-01-01

Seventy-three children with disorders of physical growth and mental development were stimulated by insulin hypoglycemia and arginine infusion and their human growth hormone (HGH) responses were determined. Only four patients exhibited absent or impaired pituitary hormone secretion and one of them presented a unique syndrome of panhypopituitarism associated with intrauterine growth retardation, long eyelashes and eyebrows, sparse hair and degeneration of the retina. Statistical analysis indicated no significant HGH peak concentrations in groups of either tall males or stunted females who possessed various sex chromosome abnormalities, nor did these groups differ in a variety of clinical parameters including age, physical growth, birth weight and intelligence. PMID:4250364

Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

PubMed Central

Gunasekaran, N; Long, LE; Dawson, BL; Hansen, GH; Richardson, DP; Li, KM; Arnold, JC; McGregor, IS

2009-01-01

Background and purpose: Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. Experimental approach: In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg·kg−1) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. Key results: ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. Conclusions and implications: The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of ‘reintoxication’ whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or ‘flashbacks’. PMID:19681888

Internet informs parents about growth hormone.

PubMed

Cousounis, Pamela; Lipman, Terri H; Ginsburg, Kenneth R; Grimberg, Adda

2013-01-01

Parents' knowledge influences decisions regarding medical care for their children. Parents of pediatric primary care patients aged 9-14 years, irrespective of height, participated in open focus groups (OFGs). Moderators asked the question, 'How do people find out about growth hormone (GH)?' Because many parents cited the Internet, the top 10 results from the Google searches of 'growth hormone children' and 'parents of children who take growth hormone' were examined. Three investigators independently performed content analysis and then reached a consensus. The results were tabulated via summary statistics. Eighteen websites were reviewed, most with the purpose of education (56%) and many funded by commercial sources (44%). GH treatment information varied, with 33% of the sites containing content only about US FDA-approved indications. Fifty-six percent of the sites included information about psychosocial benefits from treatment, with 44% acknowledging them as controversial. Although important to OFG participants, risks and costs were each omitted from 39% of the websites. Parents often turn to the Internet for GH-related information for their children, although its content may be incomplete and/or biased. Clinicians may want to provide parents with tools for critically evaluating Internet-based information, a list of prereviewed websites, or their own educational materials. Copyright © 2013 S. Karger AG, Basel.

Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

PubMed

Bahrami, A; Behzadi, Sh; Miraei-Ashtiani, S R; Roh, S-G; Katoh, K

2013-09-15

The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

PubMed

Pivnick, E K; Burstein, S; Wilroy, R S; Kaufman, R A; Ward, J C

1991-12-15

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.

Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

PubMed

Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

1998-12-01

We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

PubMed Central

Bomback, Andrew S.; Mehta, Kshama; Canetta, Pietro A.; Rao, Maya K.; Appel, Gerald B.; Radhakrishnan, Jai; Lafayette, Richard A.

2013-01-01

Summary Background and objectives Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Design, setting, participants, & measurements Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Results Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1–2.7) mg/dl, estimated GFR was 36 (28–78) ml/min per 1.73 m2, and urine protein-to-creatinine ratio was 4595 (2200–8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Conclusions Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy. PMID:24009220

Gonadotrophin-releasing activity of neurohypophysial hormones: II. The pituitary oxytocin receptor mediating gonadotrophin release differs from that of corticotrophs.

PubMed

Evans, J J; Catt, K J

1989-07-01

Neurohypophysial hormones stimulate gonadotrophin release from dispersed rat anterior pituitary cells in vitro, acting through receptors distinct from those which mediate the secretory response to gonadotrophin-releasing hormone (GnRH). The LH response to oxytocin was not affected by the presence of the phosphodiesterase inhibitor, methyl isobutylxanthine, but was diminished in the absence of extracellular calcium and was progressively increased as the calcium concentration in the medium was raised to normal. In addition, the calcium channel antagonist, nifedipine, suppressed oxytocin-stimulated secretion of LH. It is likely that the mechanisms of LH release induced by GnRH and neurohypophysial hormones are similar, although stimulation of gonadotrophin secretion is mediated by separate receptor systems. Oxytocin was more active than vasopressin in releasing LH, but less active in releasing ACTH. The highly selective oxytocin agonist, [Thr4,Gly7]oxytocin, elicited concentration-dependent secretion of LH but had little effect on corticotrophin secretion. The neurohypophysial hormone antagonist analogues, [d(CH2)5Tyr(Me)2]vasopressin, [d(CH2)5Tyr(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2Val4,Cit8]vasopressin, inhibited the LH response to both oxytocin and vasopressin. However, [d(CH2)5Tyr(Me)2]vasopressin was much less effective in inhibiting the ACTH response to the neurohypophysial hormones, and [d(CH2)5Tyr-(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2,Val4,Cit8]vasopressin exhibited no inhibitory activity against ACTH release. Thus, agonist and antagonist analogues of neurohypophysial hormones display divergent activities with regard to LH and ACTH responses, and the neuropeptide receptor mediating gonadotroph activation is clearly different from that on the corticotroph. Whereas the corticotroph receptor is a vasopressin-type receptor an oxytocin-type receptor is responsible for gonadotrophin release by neurohypophysial hormones.

Effect of growth hormone on fatty liver in panhypopituitarism

PubMed Central

Takano, S.; Kanzaki, S.; Sato, M.; Kubo, T.; Seino, Y.

1997-01-01

Accepted 10 March 1997
 A 17 year old boy was admitted because of short stature and hepatomegaly. He was diagnosed with panhypopituitarism and fatty liver. The fatty liver improved, not with hydrocortisone or levothyroxine treatment, but with growth hormone administration. The fatty liver in this patient was attributable to a growth hormone deficient state.

 PMID:9245856

Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

PubMed

Chang, Chung-Hsun; Tsai, Wen-Chung; Hsu, Ya-Hui; Pang, Jong-Hwei Su

2014-11-19

BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon.

Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 2; Hypothalamic Growth Hormone-Releasing Factor, Somatostatin Immunoreactivity, and Messenger RNA Levels in Microgravity

NASA Technical Reports Server (NTRS)

Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

1994-01-01

Immunohistochemical analyses of hypothalamic hormones carried out on tissue from rats flown on an earlier flight (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. We found that staining in the median eminence for peptides that provide both stimulatory (growth hormone-releasing factor, or GRF) and inhibitory (somatostatin, SS) influences on growth hormone secretion were depressed in flight animals relative to synchronous controls, while staining for other neuroendocrine peptides, cortocotropin-releasing factor and arginine vasopressin, were similar in these two groups. While this suggests some selective impact of weightlessness on the two principal central nervous system regulators of growth hormone dynamics, the fact that both GRF- and SS-immunoreactivity (IR) appeared affected in the same direction is somewhat problematic, and makes tentative any intimation that effects on CNS control mechanisms may be etiologically significant contributors to the sequelae of reduced growth hormone secretion seen in prolonged space flight. To provide an additional, and more penetrating, analysis we attempted in hypothalamic material harvested from animals flown on Cosmos 2044 to complement immunohistochemical analyses of GRF and SS staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

Effects of 𝛽-Hydroxy-𝛽-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training

PubMed Central

Asadi, Abbas; Arazi, Hamid

2017-01-01

Background: β-Hydroxy-β-methylbutyrate-free acid (HMB-FA) has been ingested prior to exercise to reduce muscle damage, however the effects of HMB-FA supplementation on hormonal, strength and power adaptation are unclear. Methods: Sixteen healthy men were matched and randomized into two groups and performed six-week resistance training while supplementing with either HMB-FA or placebo (3 g per day). The subjects were evaluated for 1 repetition maximum (1RM) bench press and leg press and vertical jump (VJ) prior to and after training intervention. In addition, blood samples were obtained before and after resistance training to evaluate resting growth hormone (GH), insulin like growth factor 1 (IGF-1), testosterone (TEST), cortisol (CORT), and adrenocorticotropic hormone (ACTH) responses. The HMB-FA supplementation group showed greater gains compared with the placebo group in peak power (effect size ES = 0.26 vs. 0.01) and 1RM leg press (ES = 1.52 vs. 0.96). In addition, the HMB-FA supplementation group indicated greater decrements in ACTH and CORT responses to training in comparison to the placebo group (p < 0.05). Likewise, in GH (ES = 1.41 vs. 0.12) and IGF-1 (ES = 0.83 vs. 0.41), the HMB-FA indicated greater training effects when compared with the placebo group. Conclusions: These findings provide further support for the potential anabolic benefits associated with HMB-FA supplementation. PMID:29207472

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

PubMed

Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

2011-06-01

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Hormonal characteristics of free-ranging female lions (Panthera leo) of the Serengeti Plains and Ngorongoro Crater.

PubMed

Brown, J L; Bush, M; Packer, C; Pusey, A E; Monfort, S L; O'Brien, S J; Janssen, D L; Wildt, D E

1993-01-01

Pituitary responses to gonadotrophin-releasing hormone (GnRH) and prolactin and steroid secretory profiles were examined in two populations of adult, female lions in the Serengeti (one outbred in the Serengeti Plains and one inbred in the Ngorongoro Crater) to determine whether reductions in genetic variability adversely affected endocrine function. GnRH-induced gonadotrophin secretion was also examined after adrenocorticotrophic hormone (ACTH) treatment to determine whether acute increases in serum cortisol altered pituitary function. Anaesthetized lions were administered (i) saline i.v. after 10 and 100 min of blood sampling, (ii) saline at 10 min and GnRH (1 micrograms kg-1 body weight) after 100 min; or (iii) ACTH (3 micrograms kg-1) at 10 min and GnRH after 100 min of sampling. Basal serum cortisol and basal and GnRH-induced gonadotrophin secretion were similar (P > 0.05) between females of the Ngorongoro Crater and Serengeti Plains. After ACTH, serum cortisol increased two- to threefold over baseline values and the response was unaffected (P > 0.05) by location. ACTH-induced increases in serum cortisol had no effect on subsequent basal or GnRH-stimulated luteinizing hormone (LH) or follicle-stimulating hormone (FSH) secretion. Overall mean serum progesterone concentrations ranged from 0.2 to 5.4 ng ml-1 with the exception of four females (two in the Serengeti and two in the Crater; progesterone range, 18.4-46.5 ng ml-1) that were presumed pregnant (three of these females were observed nursing cubs several weeks later).(ABSTRACT TRUNCATED AT 250 WORDS)

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

PubMed

Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W

2018-05-02

Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of

Effects of microgravity on growth hormone concentration and distribution in plants

NASA Technical Reports Server (NTRS)

Schulze, Aga; Jensen, Philip; Desrosiers, Mark; Bandurski, Robert S.

1989-01-01

On earth, gravity affects the distribution of the plant growth hormone, indole-3-acetic acid (IAA), in a manner such that the plant grows into a normal vertical orientation (shoots up, roots down). How the plant controls the amount and distribution of IAA is only partially understood and is currently under investigation in this laboratory. The question to be answered in the flight experiment concerns the effect of gravity on the concentration, turn over, and distribution of the growth hormone. The answer to this question will aid in understanding the mechanism by which plants control the amount and distribution of growth hormone. Such knowledge of a plant's hormonal metabolism may aid in the growth of plants in space and will lead to agronomic advances.

Bartter syndrome and growth hormone deficiency: three cases.

PubMed

Buyukcelik, Mithat; Keskin, Mehmet; Kilic, Beltinge Demircioglu; Kor, Yilmaz; Balat, Ayse

2012-11-01

Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, salt loss, and metabolic alkalosis. Short stature is one of the clinical manifestations in these children. Although polyuria, polydipsia, hypokalemia, and salt loss may be responsible for growth retardation, the exact pathogenesis of short stature in Bartter syndrome is not known. In this study, we present three children diagnosed as having Bartter syndrome with short stature and growth hormone (GH) deficiency. After recombinant human growth hormone therapy (rhGH), their growth velocities were improved. These results indicate that GH deficiency may contribute to short stature in children with Bartter syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with this syndrome whose condition is resistant to conventional therapies in terms of growth.

Metabolic health of young adults who were born small for gestational age and treated with growth hormone, after cessation of growth hormone treatment: a 5-year longitudinal study.

PubMed

van der Steen, Manouk; Smeets, Carolina C J; Kerkhof, Gerthe F; Hokken-Koelega, Anita C S

2017-02-01

Growth hormone treatment reduces fat mass and insulin sensitivity and increases lean body mass. Data are only available for short-term longitudinal changes after cessation of growth hormone treatment in young adults born small for gestational age. We aimed to assess long-term changes over a 5-year period following cessation of growth hormone treatment. We did a longitudinal study of young adults born small for gestational age and previously treated with growth hormone. Individuals were followed up for 5 years after attainment of adult height, when growth hormone treatment was discontinued: assessments were done at cessation of growth hormone treatment and at 6 months, 2 years, and 5 years thereafter. Data 5 years after cessation of growth hormone were compared with untreated age-matched controls. We used dual-energy x-ray absorptiometry to assess body composition, and did frequently sampled intravenous glucose tolerance tests to assess insulin sensitivity, acute insulin response, and the disposition index (a measure of β-cell function). This study is registered with ISRCTN, numbers ISRCTN96883876 and ISRCTN65230311. Between April, 2004, and April, 2016, we followed up 199 young adults born small for gestational age and previously treated with growth hormone, during the 5 years after cessation of growth hormone treatment. Data at 5 years for these individuals were compared with those for 51 untreated adults born small for gestational age with short stature, 92 untreated adults born small for gestational age with spontaneous catch-up growth, and 142 adults born appropriate for gestational age and unexposed to growth hormone treatment. In young adults born small for gestational age and previously treated with growth hormone, 5 years after cessation of growth hormone treatment, there were increases in fat mass (estimated marginal mean 10·73 kg [95% CI 9·95-11·50] at cessation of treatment vs 16·12 kg [14·77-17·46] at 5 years; p<0·0001), trunk fat (5·34 kg [4�

Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction

PubMed Central

Kanashiro-Takeuchi, Rosemeire M.; Tziomalos, Konstantinos; Takeuchi, Lauro M.; Treuer, Adriana V.; Lamirault, Guillaume; Dulce, Raul; Hurtado, Michael; Song, Yun; Block, Norman L.; Rick, Ferenc; Klukovits, Anna; Hu, Qinghua; Varga, Jozsef L.; Schally, Andrew V.; Hare, Joshua M.

2010-01-01

Whether the growth hormone (GH)/insulin-like growth factor 1(IGF-1) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth hormone-releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-1 independent fashion. After experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4-week period, either placebo (n = 14), rat recombinant GH (n = 8) or JI-38 (n = 8; 50 µg/kg per day), a potent GHRH agonist. JI-38 did not elevate serum levels of GH or IGF-1, but it markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, and circulating GH and IGF-1, but it did not offset the decline in cardiac structure and function. Whereas both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased antiapoptotic gene expression. The receptor for GHRH was detectable on myocytes, supporting direct activation of cardiac signal transduction. Collectively, these findings demonstrate that within the heart, GHRH agonists can activate cardiac repair after MI, suggesting the existence of a potential signaling pathway based on GHRH in the heart. The phenotypic profile of the response to a potent GHRH agonist has therapeutic implications. PMID:20133784

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

PubMed Central

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Plasma adrenocorticotropic hormone but not aldosterone is correlated with blood pressure in patients with aldosterone-producing adenomas.

PubMed

Kobayashi, Hiroki; Haketa, Akira; Takahiro, Ueno; Otsuka, Hiromasa; Tanaka, Sho; Hatanaka, Yoshinari; Ikeda, Yukihiro; Abe, Masanori; Fukuda, Noboru; Soma, Masayoshi

2017-03-01

Although plasma aldosterone concentration (PAC) varies depending on primary aldosteronism (PA) subtypes, patients with different subtypes may have similar blood pressure (BP). The authors hypothesized that hormones other than aldosterone might influence BP in PA patients. A total of 73 PA cases, including 30 cases of aldosterone-producing adenomas (APAs), 29 cases of bilateral hyperaldosteronism, and 24 control cases of essential hypertension were enrolled retrospectively. The authors examined the levels of aldosterone, cortisol, renin, and adrenocorticotropic hormone (ACTH) measured at 12 am, 6 am, 12 pm, and 6 pm and BP in the early morning (6 am to 7 am), late morning (9 am to 11 am), and early evening (5 pm to 7 pm). Results showed no statistically significant correlation between PAC and BP in the patients with PA; however, early and late morning systolic BP strongly correlated with ACTH at 6 am in patients with APA. These results suggest that hormones other than aldosterone, such as ACTH, may affect BP in patients with APA. ©2016 Wiley Periodicals, Inc.

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.

Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

PubMed

Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S

2014-01-01

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report

PubMed Central

2013-01-01

Introduction Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Case presentation Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. Conclusions The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome. PMID:24377430

Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report.

PubMed

Adachi, Masanori; Tajima, Toshihiro; Muroya, Koji; Asakura, Yumi

2013-12-30

Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome.

[Use of recombinant Human Growth Hormone (rHGH)].

PubMed

Calzada-León, Raúl

2017-01-01

Recombinant human growth hormone, synthesized in E.coli or mammalian cells cultures, is since 1985, a useful therapeutic resource to increase growth velocity and final height. In this paper are discussed the four phases (aims, security and efficacy, utility and efficiency) indispensables to define the start of treatment, as well as the absolute, relative and metabolic indications and the transitory and permanent conditions that contraindicate its use. It is commented the way to optimize the results (simple but indispensables indications for the physician, the patients and their family). Finally it is analyzed the results of treatment in patients with growth hormone deficiency, Turner syndrome, chronic renal failure, Prader-Willi syndrome, Noonan syndrome, SHOX deficiency, intrauterine growth retardation and idiopathic short stature.

Analysis of therapeutic growth hormone preparations: report of an interlaboratory collaborative study on growth hormone assay methodologies.

PubMed

Bristow, A F; Jeffcoate, S L

1992-09-01

Recombinant DNA-derived human growth hormone (somatotropin) is widely used to treat growth hormone-deficient children. The potency of this product is determined by in-vivo bioassay in hypophysectomized rats, which is imprecise, costly and invasive, and there have been suggestions that it could safely be replaced with in-vitro or physico-chemical alternatives. In this report we present the results of a collaborative study designed to test this proposal. Somatotropin was modified by mild or severe proteolysis, mild or severe oxidation or treatment at high pH, and compared in a multi-centre collaborative study with unmodified somatotropin or with dimerized somatotropin. Participating laboratories included manufacturers and national control laboratories, and pharmacopoeial bioassays were compared with in-house in-vitro and physico-chemical bioassays. Although performing adequately with untreated somatotropin, for degraded samples the in-vivo bioassays were relatively unresponsive to changes in the growth hormone molecule. In contrast, the physico-chemical assays, in particular the reverse-phase HPLC, performed with a high degree of selectivity. We conclude that in the case of somatotropin, the in-vivo bioassay can be removed from the routine product specification with an acceptable degree of security. This however does not obviate the requirement rigorously to demonstrate biological activity in-vivo during product development, nor may the conclusions of this study be applied to other therapeutic recombinant proteins without similar collaborative investigations.

The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

PubMed

Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

2017-12-06

Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Onset, Timing, and Exposure Therapy of Stress Disorders: Mechanistic Insight from a Mathematical Model of Oscillating Neuroendocrine Dynamics (Open Access)

DTIC Science & Technology

2016-03-25

peptide hormones such as corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by circulating glucocorticoids such as cortisol (CORT...As for many other hormones such as gonadotropin- releasing hormone (GnRH), insulin, and growth hormone (GH), the ultradian release pattern of...therapy; GH: growth hormone ; GnRH: gonadotropin-releasing hormone ; GR: glucocorticoid receptors; MDD: major depressive disorder; hnRNA: heterogeneous

The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects

PubMed Central

Dehkhoda, Farhad; Lee, Christine M. M.; Medina, Johan; Brooks, Andrew J.

2018-01-01

The growth hormone receptor (GHR), although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK–STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling. PMID:29487568

Hormone-Mediated Pattern Formation in Seedling of Plants: a Competitive Growth Dynamics Model

NASA Astrophysics Data System (ADS)

Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Oikawa, Noriko; Okabe, Hirotaka; Kai, Shoichi

2001-10-01

An ecologically relevant pattern formation process mediated by hormonal interactions among growing seedlings is modeled based on the experimental observations on the effects of indole acetic acid, which can act as an inhibitor and activator of root growth depending on its concentration. In the absence of any lateral root with constant hormone-sensitivity, the edge effect phenomenon is obtained depending on the secretion rate of hormone from the main root. Introduction of growth-stage-dependent hormone-sensitivity drastically amplifies the initial randomness, resulting in spatially irregular macroscopic patterns. When the lateral root growth is introduced, periodic patterns are obtained whose periodicity depends on the length of lateral roots. The growth-stage-dependent hormone-sensitivity and the lateral root growth are crucial for macroscopic periodic-pattern formation.

Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

PubMed Central

Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

2009-01-01

While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

NASA Technical Reports Server (NTRS)

Meehan, R. T.

1986-01-01

Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

Growth hormone and the heart.

PubMed

Cittadini, A; Longobardi, S; Fazio, S; Saccà, L

1999-01-01

Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.

Novel growth hormone receptor gene mutation in a patient with Laron syndrome.

PubMed

Arman, Ahmet; Yüksel, Bilgin; Coker, Ajda; Sarioz, Ozlem; Temiz, Fatih; Topaloglu, Ali Kemal

2010-04-01

Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation.

Association of hormonal responses and performance of student pilots during acceleration training on the human centrifuge

NASA Astrophysics Data System (ADS)

Wirth, D.; Rohleder, N.; Welsch, H.

2005-08-01

Prediction of student pilots' +Gz tolerance by stress hormone levels would be a useful tool in aviation medicine. The aim of the present study was to analyze the relationship between neuroendocrine parameters with performance during acceleration training on the human centrifuge (HC).We investigated 21 student pilots during self-controlled acceleration training on the HC. Adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine were measured after individual training sessions and at rest. Performance was defined by several characteristics including maximum tolerated acceleration. ACTH and cortisol, were significantly higher 20 minutes after acceleration training compared to the resting condition. Subjects tolerated a maximal acceleration of +6.69 Gz. HPA hormone levels and responses were associated with maximum tolerated acceleration +Gz. These findings support the expectation that acceleration- induced increases in stress hormones may enable the organism to tolerate a higher acceleration and could therefore be used as predictors for acceleration tolerance.

Do growth hormone-releasing peptides act as ghrelin secretagogues?

PubMed

Ahnfelt-Rønne, I; Nowak, J; Olsen, U B

2001-02-01

NN703 is an orally active and selective growth hormone secretagogue (GHS) that was derived from growth hormone-releasing peptide-1(GHRP-1) via ipamorelin by a peptidomimetic approach and has now entered into phase II clinical trials. When the disposition in rats of NN703 and GHRP-6 was studied using whole-body autoradiography following administration of an iv dose of radiolabeled material, we found that a substantial amount of these secretagogues accumulate in the glandular part of the stomach. Because this is the site of synthesis and secretion of ghrelin, the endogenous GHS, we investigated the effect of resection of the gastrointestinal (GI) tract on growth hormone (GH) release induced by GHRP-6. This procedure significantly attenuated the GH secretion response by 60-70%. By contrast, the effect of GH-releasing hormone on GH release was not inhibited. The binding of GHRPs to the glandular part of the stomach and the blunted GH response to GHRP-6 following resection of the GI tract suggest a role for ghrelin as a mediator of part of the GH-releasing effect of GHRPs.

Growth hormone deficiency: an update.

PubMed

Audí, L; Fernández-Cancio, M; Camats, N; Carrascosa, A

2013-03-01

Growth hormone (GH) deficiency (GHD) in humans manifests differently according to the individual developmental stage (early after birth, during childhood, at puberty or in adulthood), the cause or mechanism (genetic, acquired or idiopathic), deficiency intensity and whether it is the only pituitary-affected hormone or is combined with that of other pituitary hormones or forms part of a complex syndrome. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise mutation types and mechanisms for previously described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic, although less frequently when they are congenital and/or familial. The clinical and biochemical diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, probably because the diagnosis based on the so-called GH secretion stimulation tests will prove to be of limited usefulness for predicting therapy indications.

Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

PubMed Central

Schaefer, G B; Rosenbloom, A L; Guevara-Aguirre, J; Campbell, E A; Ullrich, F; Patil, K; Frias, J L

1994-01-01

Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency. Images PMID:7815422

Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

PubMed

Botticelli, G; Bacchi Modena, A; Bresciani, D; Villa, P; Aguzzoli, L; Florio, P; Nappi, R E; Petraglia, F; Genazzani, A R

1992-12-01

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.

PubMed

Lan, Hainan; Zheng, Xin; Khan, Muhammad Akram; Li, Steven

2015-11-01

In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diacylglycerol production induced by growth hormone in Ob1771 preadipocytes arises from phosphatidylcholine breakdown

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

Catalioto, R.M.; Ailhaud, G.; Negrel, R.

1990-12-31

Growth Hormone has recently been shown to stimulate the formation of diacylglycerol in Ob1771 mouse preadipocyte cells without increasing inositol lipid turnover. Addition of growth hormone to Ob1771 cells prelabelled with ({sup 3}H)glycerol or ({sup 3}H)choline led to a rapid, transient and stoechiometric formation of labelled diacylglycerol and phosphocholine, respectively. In contrast, no change was observed in the level of choline and phosphatidic acid whereas the release of water-soluble metabolites in ({sup 3}H)ethanolamine prelabelled cells exposed to growth hormone was hardly detectable. Stimulation by growth hormone of cells prelabelled with (2-palmitoyl 9, 10 ({sup 3}H))phosphatidylcholine also induced the production ofmore » labelled diacyglycerol. Pertussis toxin abolished both diacylglycerol and phosphocholine formation induced by growth hormone. It is concluded that growth hormone mediates diacylglycerol production in Ob1771 cells by means of phosphatidylcholine breakdown involving a phospholipase C which is likely coupled to the growth hormone receptor via a pertussis toxin-sensitive G-protein.« less

Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

PubMed

Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

2016-07-01

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

Attenuation of Posttraumatic Muscle Catabolism and Osteopenia by Long-Term Growth Hormone Therapy

PubMed Central

Hart, David W.; Herndon, David N.; Klein, Gordon; Lee, Steven B.; Celis, Mario; Mohan, Subburaman; Chinkes, David L.; Wolf, Steven E.

2001-01-01

Objective To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn. Summary Background Data The hypermetabolic response to severe burn is associated with increased energy expenditure, insulin resistance, immunodeficiency, and whole body catabolism that persists for months after injury. Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses. Methods Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth. Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were compared between groups. Results Growth hormone subjects gained more weight than placebo subjects at the 9-month study point; this disparity in weight gain continued to expand throughout the remainder of the study. Height also increased in the growth hormone group compared with controls at 12 months. Change in lean body mass was greater in those treated with growth hormone at 6, 9, and 12 months. Bone mineral content was increased at 9 and 12 months; this was associated with higher parathormone levels. Conclusions Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn. PMID:11371741

Insulin-like growth factor 1 (IGF-1): a growth hormone

PubMed Central

Laron, Z

2001-01-01

Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Therapeutic benefits of ACTH and levetiracetam in STXBP1 encephalopathy with a de novo mutation: A case report and literature review.

PubMed

Liu, Shunli; Wang, Liyuan; Cai, Xiao Tang; Zhou, Hui; Yu, Dan; Wang, Zhiling

2018-05-01

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation. Early-onset epileptic encephalopathy with STXBP1 mutation. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Effect of growth hormone treatment on craniofacial growth in children: Idiopathic short stature versus growth hormone deficiency.

PubMed

Choi, Sung-Hwan; Fan, Dong; Hwang, Mi-Soo; Lee, Hee-Kyung; Hwang, Chung-Ju

2017-04-01

Few studies have evaluated craniofacial growth in boys and girls with idiopathic short stature (ISS) during growth hormone (GH) treatment. The aim of this study was to evaluate the effect of GH treatment on craniofacial growth in children with ISS, compared with those with growth hormone deficiency (GHD). This study included 36 children (mean age, 11.3 ± 1.8 years) who were treated with GH consecutively. Lateral cephalograms were analyzed before and 2 years after start of GH treatment. There were no significant differences in age and sex between ISS and GHD groups and the reference group from semilongitudinal study (10 boys and 8 girls from each group). Before treatment, girls with ISS showed a skeletal Class II facial profile compared with the GHD and reference groups (p = 0.003). During GH treatment, the amount of maxillary length increased beyond norm in the ISS and GHD groups in boys (p = 0.035) > 3 standard deviation score (SDS). Meanwhile, mandibular ramus height (p = 0.001), corpus length, and total mandibular length (p = 0.007 for both) increased more in girls with ISS than in girls with GHD. Lower and total anterior facial heights increased more in girls with ISS than in girls with GHD (p = 0.021 and p = 0.007, respectively), > 7-11 SDS. GH should be administered carefully when treating girls with ISS, because GH treatment has great effects on vertical overgrowth of the mandible and can result in longer face. Copyright © 2016. Published by Elsevier B.V.

Levels of plasma and fecal glucocorticoid metabolites following an ACTH challenge in male and female coyotes (Canis latrans).

PubMed

Stevenson, Erika T; Gese, Eric M; Neuman-Lee, Lorin A; French, Susannah S

2018-03-01

Knowledge of endocrine stress responses can be advantageous for understanding how animals respond to their environment. One tool in wildlife endocrinology is to measure the adrenocortical activity as a parameter of disturbance of animals. Fecal glucocorticoid metabolites (GCMs) provide a noninvasive assessment of adrenocortical activity. Using an adrenocorticotropic hormone (ACTH) challenge administered to 28 captive coyotes (Canis latrans), we measured the levels of plasma cortisol, and fecal cortisol and corticosterone metabolites (i.e., GCMs). Our goal was to determine the dose-response in the plasma and fecal samples following the injection and determine if there were effects of sex, age, and time of day. Specifically, animals were anesthetized for ~ 90 min with treatment animals intravenously injected with exogenous ACTH and control animals receiving saline. We collected blood samples prior to injection and at 4 different time points post-injection. We also collected fecal samples 2 days pre- and 2 days post-injection to measure fecal GCMs and determine if an endocrine stress response could be detected in fecal samples. We found a definite response in cortisol levels in the plasma for coyotes to the ACTH challenge. There was a response in fecal corticosterone 1 day post-injection, but the control males showed a similar response indicating a handling effect. Fecal cortisol levels did not indicate a response to the ACTH challenge, and were significantly lower than corticosterone concentrations. We also found significant sex, but not age or diurnal, differences in fecal GCMs. Radioimmunoassays for fecal corticosterone levels appeared to be a reliable indicator of physiological stress in coyotes.

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

PubMed Central

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

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/.

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

PubMed

Witkowska-Sędek, Ewelina; Rumińska, Małgorzata; Stelmaszczyk-Emmel, Anna; Majcher, Anna; Pyrżak, Beata

2018-01-01

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.

On the mode of action of ACTH on the isolated perfused adrenal gland

PubMed Central

Jaanus, Siret D.; Rosenstein, M. J.; Rubin, R. P.

1970-01-01

1. Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied. 2. Steroid outputs varied with the ACTH concentration, as well as with the duration of exposure to a given ACTH concentration. 3. Omission of calcium from the perfusion medium markedly depressed ACTH-evoked steroid release. The steroid output was directly related to the extracellular calcium concentration up to 0·5 mM. 4. During a constant exposure to ACTH, steroid output was maintained for at least 2-3 hr, provided that calcium was present in the perfusion medium. 5. Strontium, but not barium or magnesium, replaced calcium in maintaining the secretory response to ACTH. 6. Magnesium depressed ACTH-evoked secretion in the presence of calcium, and this depression of secretion was antagonized by increasing the calcium concentration. 7. Prolonged perfusion with sodium-free or potassium-free solutions did not markedly inhibit steroid output in response to ACTH. Excess potassium (56 mM) did not produce a consistent or marked increase in spontaneous steroid output and did not affect the response to ACTH. 8. The steroid content of adrenal glands perfused with Locke solution and exposed to ACTH was about 10% of the amount which was secreted. By contrast, adrenal glands perfused with calcium-free media and exposed to ACTH contained much higher amounts of steroid, despite the negligible amount secreted. 9. These data suggest that calcium plays a critical role in the mechanism of corticosteroid secretion from the adrenal cortex. PMID:4322584

Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province, China.

PubMed

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Han, Guangen; Wang, Xiaofeng

2014-11-15

Increased electronic waste (e-waste) has raised public concerns regarding exposure to numerous toxic contaminants, particularly polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). In China, the body burdens of PCBs, PBDEs and PCDD/Fs are associated with thyroid hormones in populations from e-waste dismantling sites; however, it is unclear whether this association occurs in children. In this study, we determined the serum levels of PCBs, PBDEs and PCDD/Fs and the endocrine hormones including free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) in 21 children from an e-waste dismantling area and 24 children from a control area. The results showed that the mean levels of ∑PCBs and ∑PBDEs in the exposure group were significantly higher than in the control group (40.56 and 32.09 ng g(-1) lipid vs. 20.69 and 8.43 ng g(-1) lipid, respectively, p<0.01 for each), and the mean level of ∑PCDD/Fs in the exposure group was higher than in the control group, but the difference was not significant (206.17 vs. 160.27 pg g(-1) lipid, p>0.05). For the endocrine hormones, we did not find significant differences between the exposed and control groups, although the mean levels of FT3, TT3, TT4, ACTH, cortisol and GH were higher, whereas the mean levels of FT4 and TSH were lower in the exposed group. The mean level of ∑PBDEs was positively correlated with the mean levels of ∑PCBs (r=0.60, p<0.05) and ∑PCDD/Fs (r=0.61, p<0.05). Furthermore, the mean level of ∑PBDEs was positively correlated with ACTH (r=0.61, p<0.05). In conclusion, our data suggested that exposure to e-waste dismantling environment increased the body burdens of PCBs and PBDEs in local children and that these contaminants released from the e-waste might contribute to

Novel orally active growth hormone secretagogues.

PubMed

Hansen, T K; Ankersen, M; Hansen, B S; Raun, K; Nielsen, K K; Lau, J; Peschke, B; Lundt, B F; Thøgersen, H; Johansen, N L; Madsen, K; Andersen, P H

1998-09-10

A novel class of growth hormone-releasing compounds with a molecular weight in the range from 500 to 650 has been discovered. The aim of this study was to obtain growth hormone secretagogues with oral bioavailability. By a rational approach we were able to reduce the size of the lead compound ipamorelin (4) and simultaneously to reduce hydrogen-bonding potential by incorporation of backbone isosters while retaining in vivo potency in swine. A rat pituitary assay was used for screening of all compounds and to evaluate which compounds should be tested further for in vivo potency in swine and oral bioavailability, fpo, in dogs. Most of the tested compounds had fpo in the range of 10-55%. In vivo potency in swine after iv dosing is reported, and ED50 was found to be 30 nmol/kg of body weight for the most potent compound.

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

PubMed

Köster, L S; Schoeman, J P; Meltzer, D G A

2007-09-01

Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001). There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867). Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

Growth hormone therapy in hypochondroplasia.

PubMed

Ramaswami, U; Hindmarsh, P C; Brook, C G

1999-02-01

Patients with hypochondroplasia present with variable phenotypes. Children with severe short stature and disproportion of the body segments usually have the mutation Asn540Lys. They respond to growth hormone (GH) therapy with an increase in spinal length and, coupled with a surgical leg-lengthening procedure, it is possible for some patients to achieve adult heights within the normal range. Some children who present with proportionate short stature and hypochondroplasia fail to increase their growth rate at puberty, although the growth spurt can be restored by GH therapy. Others, with an identical presentation, seem to grow normally during puberty. At present, there is no way of predicting who will undergo a normal pubertal growth spurt. We therefore monitor all patients during childhood and give GH treatment only to those patients who fail to develop a growth spurt at puberty. Severe cases may occasionally need treatment before puberty if their growth velocity is compromised, but these will probably also be candidates for a surgical leg-lengthening procedure.

Growth hormone and early treatment.

PubMed

Antoniazzi, F; Cavarzere, P; Gaudino, R

2015-06-01

Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.

Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion.

PubMed

Iranmanesh, Ali; Veldhuis, Johannes D

2008-11-01

ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (P<0.001). Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced cortisol depletion (P=0.020). ACTH secretory-burst shape and half-life were stable. ApEn of ACTH release declined overnight (P=0.021) and with the drug (P=0.001), denoting enhanced feedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging.

Influence of estradiol and androstenedione on ACTH and cortisol secretion in the ovine fetus.

PubMed

Wood, C E; Saoud, C J

1997-01-01

To test the hypothesis that physiologic increases in fetal plasma 17 beta-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Seventeen pregnant ewes and their fetuses were chronically catheterized. At the time of surgery, the fetuses received implants that released 17 beta-estradiol (n = 5) alone or 17 beta-estradiol and androstenedione (n = 6), each at a rate of approximately 250 micrograms/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a "placebo" pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17 beta-estradiol and androstenedione. Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17 beta-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05). Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.

The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.

PubMed

Baumann, G; Maheshwari, H

1997-11-01

We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone-releasing hormone receptor (GHRH-R) locus on chromosome 7. Amplification and sequencing of the GHRH-R gene in affected subjects demonstrated an amber nonsense mutation (GAG-->TAG; Glu50-->Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH-R in its extracellular domain, which is likely to result in a severely disabled or non-existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone-releasing hormone (GHRH)--growth hormone--insulin-like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH-R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.

Immunocytochemical location of pituitary cells containing ACTH, alpha-MSH, and beta-endorphin in Acipenser transmontanus, Lepisosteus spatula, and Amia calva.

PubMed

Joss, J M; Dores, R M; Crim, J W; Beshaw, M

1990-06-01

This immunocytochemical study of the pituitaries of the primitive actinopterygians, Acipenser transmontanus, Lepisosteus spatula, and Amia calva, showed a strict delineation between the hormonal fragments of proopiomelanocorticotropin (POMC) produced by corticotropes of the pars distalis and the melanotropes of the pars intermedia. Corticotropes were immunoreactive only for ACTH and not to either of the further degradation products, alpha-MSH or beta-endorphin. Melanotropes were shown to be immunoreactive to all three antisera but it is argued that immunoreactivity of melanotropes to ACTH antiserum is due to that antiserum's cross-reactivity with the cleavage product corticotropin-like intermediate peptide. The PAS positivity of both the corticotropes and the melanotropes of all three primitive fish argues for an ancient origin of a carbohydrate component of POMC and for its loss or reduction in teleosts where these cells are PAS negative.

Intestinal hormones and growth factors: Effects on the small intestine

PubMed Central

Drozdowski, Laurie; Thomson, Alan BR

2009-01-01

There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids. PMID:19152442

Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells

NASA Astrophysics Data System (ADS)

Morgan, Jeffrey R.; Barrandon, Yann; Green, Howard; Mulligan, Richard C.

1987-09-01

Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.

Effects of Plant Growth Hormones on Mucor indicus Growth and Chitosan and Ethanol Production.

PubMed

Safaei, Zahra; Karimi, Keikhosro; Golkar, Poorandokht; Zamani, Akram

2015-07-22

The objective of this study was to investigate the effects of indole-3-acetic acid (IAA) and kinetin (KIN) on Mucor indicus growth, cell wall composition, and ethanol production. A semi-synthetic medium, supplemented with 0-5 mg/L hormones, was used for the cultivations (at 32 °C for 48 h). By addition of 1 mg/L of each hormone, the biomass and ethanol yields were increased and decreased, respectively. At higher levels, however, an inverse trend was observed. The glucosamine fraction of the cell wall, as a representative for chitosan, followed similar but sharper changes, compared to the biomass. The highest level was 221% higher than that obtained without hormones. The sum of glucosamine and N-acetyl glucosamine (chitin and chitosan) was noticeably enhanced in the presence of the hormones. Increase of chitosan was accompanied by a decrease in the phosphate content, with the lowest phosphate (0.01 g/g cell wall) being obtained when the chitosan was at the maximum (0.45 g/g cell wall). In conclusion, IAA and KIN significantly enhanced the M. indicus growth and chitosan production, while at the same time decreasing the ethanol yield to some extent. This study shows that plant growth hormones have a high potential for the improvement of fungal chitosan production by M. indicus.

Analysis of craniofacial and extremity growth in patients with growth hormone deficiency during growth hormone therapy.

PubMed

de Faria, Maria Estela Justamante; Carvalho, Luciani R; Rossetto, Shirley M; Amaral, Terezinha Sampaio; Berger, Karina; Arnhold, Ivo Jorge Prado; Mendonca, Berenice Bilharinho

2009-01-01

There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone (GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2-11 years. GH doses (0.1-0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur. Copyright 2009 S. Karger AG, Basel.

The Physiology of Growth Hormone-Releasing Hormone (GHRH) in Breast Cancer

DTIC Science & Technology

2003-06-01

production of growth hormone-releasing factor by carcinoid and pancreatic islet tumors associated with acromegaly . Prog Clin Biol Res 1981; 74:259-271. (16...promotion of apop- cause of acromegaly . More recently, expression has been tosis. These results indicate that disruption of enaog- demonstrated in tumors

Light-Mediated Hormonal Regulation of Plant Growth and Development.

PubMed

de Wit, Mieke; Galvão, Vinicius Costa; Fankhauser, Christian

2016-04-29

Light is crucial for plant life, and perception of the light environment dictates plant growth, morphology, and developmental changes. Such adjustments in growth and development in response to light conditions are often established through changes in hormone levels and signaling. This review discusses examples of light-regulated processes throughout a plant's life cycle for which it is known how light signals lead to hormonal regulation. Light acts as an important developmental switch in germination, photomorphogenesis, and transition to flowering, and light cues are essential to ensure light capture through architectural changes during phototropism and the shade avoidance response. In describing well-established links between light perception and hormonal changes, we aim to give insight into the mechanisms that enable plants to thrive in variable light environments.

Growth Hormone Deficiency in the Transition Age.

PubMed

Loche, Sandro; Di Iorgi, Natascia; Patti, Giuseppa; Noli, Serena; Giaccardi, Marta; Olivieri, Irene; Ibba, Anastasia; Maghnie, Mohamad

2018-01-01

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations. © 2018 S. Karger AG, Basel.

The Value of Perioperative Levels of ACTH, DHEA, and DHEA-S and Tumor Size in Predicting Recurrence of Cushing Disease.

PubMed

El Asmar, Nadine; Rajpal, Aman; Selman, Warren R; Arafah, Baha M

2018-02-01

Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 μg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 μg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 μg/dL vs 2.9 ± 2.2 μg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P < 0.0001), DHEA (3.8 ± 1.7 ng/mL vs 1.2 ± 1.1 ng/mL; P = 0.005), and dehydroepiandrosterone sulphate (DHEA-S) (143.9 ± 45.2 μg/dL vs 48.9 ± 38.2 μg/dL; P < 0.0001) were higher. At nadir hypocortisolemia, perioperative ACTH levels were >20 in all REC patients and <20 ng/L in the NO-REC group. Patients with REC had larger tumors than those with NO-REC. Recurrent CD is characterized by persistent perioperative ACTH secretion after adenomectomy. Higher perioperative levels of ACTH, DHEA, and DHEA-S are highly predictive of future disease recurrence, particularly in those with profound hypocortisolemia. Copyright © 2017 Endocrine Society

Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy; Harrison, Evan; Cook-Andersen, Heidi; Duleba, Antoni J; Chang, R. Jeffrey

2016-01-01

Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. PMID:27473350

Growth enhancement in transgenic tilapia by ectopic expression of tilapia growth hormone.

PubMed

Martínez, R; Estrada, M P; Berlanga, J; Guillén, I; Hernández, O; Cabrera, E; Pimentel, R; Morales, R; Herrera, F; Morales, A; Piña, J C; Abad, Z; Sánchez, V; Melamed, P; Lleonart, R; de la Fuente, J

1996-03-01

The generation of transgenic fish with the transfer of growth hormone (GH) genes has opened new possibilities for the manipulation of growth in economically important fish species. The tilapia growth hormone (tiGH) cDNA was linked to the human cytomegalovirus (CMV) enhancer-promoter and used to generate transgenic tilapia by microinjection into one-cell embryos. Five transgenic tilapia were obtained from 40 injected embryos. A transgenic animal containing one copy of the transgene per cell was selected to establish a transgenic line. The transgene was stably transmitted to F1 and F2 generations in a Mendelian fashion. Ectopic, low-level expression of tiGH was detected in gonad and muscle cells of F1 transgenic tilapia by immunohystochemical analysis of tissue sections. Nine-month-old transgenic F1 progeny were 82% larger than nontransgenic fish at p = .001. These results showed that low-level ectopic expression of tiGH resulted in a growth acceleration in transgenic tilapia. Tilapia GH gene transfer is an alternative for growth acceleration in tilapia.

Hostile behavior during marital conflict alters pituitary and adrenal hormones.

PubMed

Malarkey, W B; Kiecolt-Glaser, J K; Pearl, D; Glaser, R

1994-01-01

We evaluated hormonal changes and problem-solving behaviors in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. The subjects were selected on the basis of stringent mental and physical health criteria, and admissions were scheduled during the follicular phase of the woman's menstrual cycle. For frequent, unobtrusive endocrine sampling during the interaction tasks, a long polyethylene tube was attached to a heparin well, allowing nurses to draw blood samples at set intervals, out of subjects' sight. Five blood samples were obtained before, during, and after a 30-minute structured problem-solving or conflict task. The conflict session was recorded on videotapes that were later scored for problem-solving behaviors using the Marital Interaction Coding System (MICS). Marital conflict and MICS-coded hostile or negative behavior during conflict was closely linked to changes in serum hormonal levels across five of the six hormones we studied, in spite of the high marital satisfaction of our newlywed couples and the healthy lifestyles demanded by our exclusion criteria. Hostile behavior was associated with decreased levels of prolactin (PRL) and increases in epinephrine (EPI), norepinephrine (NEPI), ACTH, and growth hormone (GH), but not cortisol. These data suggest that the endocrine system may be an important mediator between personal relationships and health.

Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion

PubMed Central

Iranmanesh, Ali; Veldhuis, Johannes D

2009-01-01

Background ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Hypothesis Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Subjects Seven healthy men. Interventions An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Analysis Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Results Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by ≥77 and 54% respectively (P<0.001). Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced cortisol depletion (P = 0.020). ACTH secretory-burst shape and half-life were stable. ApEn of ACTH release declined overnight (P = 0.021) and with the drug (P = 0.001), denoting enhanced feedforward coordination. Conclusion The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging. PMID:18713842

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1984-01-01

A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

Ethylene and Hormonal Cross Talk in Vegetative Growth and Development.

PubMed

Van de Poel, Bram; Smet, Dajo; Van Der Straeten, Dominique

2015-09-01

Ethylene is a gaseous plant hormone that most likely became a functional hormone during the evolution of charophyte green algae, prior to land colonization. From this ancient origin, ethylene evolved into an important growth regulator that is essential for myriad plant developmental processes. In vegetative growth, ethylene appears to have a dual role, stimulating and inhibiting growth, depending on the species, tissue, and cell type, developmental stage, hormonal status, and environmental conditions. Moreover, ethylene signaling and response are part of an intricate network in cross talk with internal and external cues. Besides being a crucial factor in the growth control of roots and shoots, ethylene can promote flowering, fruit ripening and abscission, as well as leaf and petal senescence and abscission and, hence, plays a role in virtually every phase of plant life. Last but not least, together with jasmonates, salicylate, and abscisic acid, ethylene is important in steering stress responses. © 2015 American Society of Plant Biologists. All Rights Reserved.

Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat

PubMed Central

Jeong, Sang-Hee; Kang, Daejin; Lim, Myung-Woon; Kang, Chang Soo

2010-01-01

Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented. PMID:24278538

Modulation of the neonatal pituitary and adrenocortical responses to stress by thyroid hormones in the rat: effects of hypothyroidism and hyperthyroidism.

PubMed

Walker, C D; Sizonenko, P C; Aubert, M L

1989-09-01

Neonatal rats exhibit a period of diminished pituitary and adrenocortical responses to stress during the first 2 weeks of life. Since thyroid hormones are known to affect brain development, modulation of these responses to stress by alterations in thyroid hormone status have been investigated in hypothyroid (Hypo) and hyperthyroid (Hyper) rat pups. Changes in ACTH and corticosterone (B) levels were measured under basal and stress conditions (3 min exposure to ether vapors) in neonates of various ages (day 5-21). Basal T4 and corticosterone-binding globulin (CBG) levels were also measured. Hypo pups were obtained from methimazole-treated mothers and hyperthyroidism was induced by daily subcutaneous injections of L-T4 (100 micrograms/kg BW) from birth on. In Hyper rats, premature onset of ACTH and B responses to stress was observed in 5-day-old rats while significant ACTH and B secretion only appeared by day 10 in vehicle-injected rats. By contrast, ACTH and B responses to stress were delayed in Hypo pups and only occurred by day 21. The lack of ACTH and B responses to stress of 14-day-old Hypo rats could be reversed by one single L-T4 injection (100 micrograms/kg BW) given 24 h, but not 4 h prior to exposure to stress. On day 21, smaller (p less than 0.05) stress-induced ACTH release was observed both in Hypo and Hyper rats compared to intact rats, concomitant with a diminished ACTH secretion following exogenous ovine CRF (10 micrograms/kg BW, i.p.) administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

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

Romshe, C.A.; Zipf, W.B.; Miser, A.

1984-02-01

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significantmore » differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.« less

Hypopituitarism: growth hormone and corticotropin deficiency.

PubMed

Capatina, Cristina; Wass, John A H

2015-03-01

This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Ghrelin and the growth hormone secretagogue receptor in growth and development.

PubMed

Chanoine, J-P; De Waele, K; Walia, P

2009-04-01

The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.

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.

Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat.

PubMed

Takahashi, L K; Kim, H

1995-04-01

Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum corticosterone response to adrenocorticotropic hormone stimulation in Florida sandhill cranes.

PubMed

Ludders, J W; Langenberg, J A; Czekala, N M; Erb, H N; McCormick, H

1998-10-01

Florida sandhill cranes (Grus canadensis pratensis) were conditioned to confinement in an enclosure for 7 days, 6 hr a day. On day 8, cranes were catheterized and then confined in an enclosure. Venous blood (2 ml) was collected through the catheter and an attached IV line immediately before (-60 min) and 60 min after (0 min) confinement. Using a randomization table and a restricted cross-over experimental design, cranes were injected intravenously with either saline (control) or adrenocorticotropic hormone (ACTH; cosyntropin, Cortrosyn; 0.25 mg). At 30, 60, 120, 180, 240 and 300 min after injection, blood samples were collected and assayed for corticosterone. The cranes receiving ACTH increased their serum corticosterone concentrations as much as fivefold above baseline concentrations. Serum corticosterone concentrations remained significantly elevated for approximately 60 min after ACTH stimulation. Physical restraint and catheterization caused an increase in serum corticosterone almost comparable to that induced by ACTH stimulation. In cranes injected with saline, serum corticosterone decreased within 1 hr after physical restraint and catheterization, and remained at lower levels throughout the remaining 5 hr of confinement.

Gravitational effects on plant growth hormone concentration

NASA Technical Reports Server (NTRS)

Bandurski, R. S.; Schulze, A.

1983-01-01

Dolk's (1936) finding that more growth hormone diffuses from the lower side of a gravity-stimulated plant shoot than from the upper side is presently confirmed by means of both an isotope dilution assay and selected ion monitoring-gas chromatography-mass spectrometry, and it is established that the asymmetrically distributed hormone is indole-3-acetic acid (IAA). This is the first physicochemical demonstration that there is more IAA on the lower sides of a geostimulated plant shoot. It is also found that free IAA primarily occurs in the conductive vascular tissues of the shoot, while IAA esters predominate in the growing cortical cells. A highly sensitive gas chromatographic isotope dilution assay shows that the hormone asymmetry also occurs in the nonvascular tissue.

Growth hormone deficiency in children and young adults.

PubMed

Oświęcimska, Joanna; Roczniak, Wojciech; Mikołajczak, Agata; Szymlak, Agnieszka

2016-09-13

Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

NASA Technical Reports Server (NTRS)

Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Skeletal Effects of Growth Hormone and Insulin-like Growth Factor-I Therapy

PubMed Central

Lindsey, Richard C.; Mohan, Subburaman

2015-01-01

The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis. PMID:26408965

Rooster feathering, androgenic alopecia, and hormone dependent tumor growth: What is in common?

PubMed Central

Mayer, Julie Ann; Chuong, Cheng-Ming; Widelitz, Randall

2015-01-01

Different epithelial organs form as a result of epithelial - mesenchymal interactions and share a common theme modulated by variations (Chuong edit. In Molecular Basis of Epithelial Appendage Morphogenesis, 1998). One of the major modulators is the sex hormone pathway that acts on the prototype signaling pathway to alter organ phenotypes. Here we focus on how the sex hormone pathway interfaces with epithelia morphogenesis related signaling pathways. We first survey these sex hormone regulated morphogenetic processes in various epithelial organs. Sexual dimorphism of hairs and feathers has implications in sexual selection. Diseases of these pathways result in androgenic alopecia, hirsutism, henny feathering, etc. The growth and development of mammary glands, prostate glands and external genitalia essential for reproductive function are also dependent on sex hormones. Diseases affecting these organs include congenital anomalies and hormone dependent type of breast and prostate cancers. To study the role of sex hormones in new growth in the context of system biology / pathology, an in vivo model in which organ formation starts from stem cells is essential. With recent developments (Yu et al., The morphogenesis of feathers. Nature 420:308–312, 2002), the growth of tail feathers in roosters and hens has become a testable model in which experimental manipulations are possible. We show exemplary data of differences in their growth rate, proliferative cell population and signaling molecule expression. Working hypotheses are proposed on how the sex hormone pathways may interact with growth pathways. It is now possible to test these hypotheses using the chicken model to learn fundamental mechanisms on how sex hormones affect organogenesis, epithelial organ cycling, and growth related tumorigenesis. PMID:15617560

Intra-myocardial growth hormone administration ameliorates arrhythmogenesis during ischemia-reperfusion in rats.

PubMed

Kontonika, Marianthi; Barka, Eleonora; Roumpi, Maria; Vilaeti, Agapi D; Baltogiannis, Giannis G; Vlahos, Antonios P; Agathopoulos, Simeon; Kolettis, Theofilos M

Growth hormone, currently under evaluation for the prevention of left ventricular remodeling post-myocardial infarction, displays antiarrhythmic properties in the acute setting. However, it is uncertain whether these actions are retained after ischemia/reperfusion. Using implanted telemetry transmitters, we examined the effects of prolonged, intra-myocardial growth hormone administration in conscious rats. During a 24-h observation period, ventricular tachyarrhythmias and sympathetic activation were attenuated in treated rats, whereas infarct-size was unchanged. These findings call for further study on the antiarrhythmic effects of growth hormone and on the underlying mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

A Novel Mutation in OTX2 Causes Combined Pituitary Hormone Deficiency, Bilateral Microphthalmia, and Agenesis of the Left Internal Carotid Artery.

PubMed

Shimada, Aya; Takagi, Masaki; Nagashima, Yuka; Miyai, Kentaro; Hasegawa, Yukihiro

2016-01-01

Mutations in OTX2 cause hypopituitarism, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency (CPHD), which are commonly detected in association with severe eye abnormalities, including anophthalmia or microphthalmia. Pituitary phenotypes of OTX2 mutation carriers are highly variable; however, ACTH deficiency during the neonatal period is not common in previous reports. We report a novel missense OTX2 (R89P) mutation in a CPHD patient with severe hypoglycemia in the neonatal period due to ACTH deficiency, bilateral microphthalmia, and agenesis of the left internal carotid artery (ICA). We identified a novel heterozygous mutation in OTX2 (c.266G>C, p.R89P). R89P OTX2 showed markedly reduced transcriptional activity of HESX1 and POU1F1 reporters compared with wild-type OTX2. A dominant negative effect was noted only in the transcription analysis with POU1F1 promoter. Electrophoretic mobility shift assay experiments showed that R89P OTX2 abrogated DNA-binding ability. OTX2 mutations can cause ACTH deficiency in the neonatal period. Our study also shows that OTX2 mutations are associated with agenesis of the ICA. To the best of our knowledge, this is the first report of a transcription factor gene mutation, which was identified due to agenesis of the ICA of a patient with CPHD. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in OTX2. © 2016 S. Karger AG, Basel.

Testicular descent related to growth hormone treatment.

PubMed

Papadimitriou, Anastasios; Fountzoula, Ioanna; Grigoriadou, Despina; Christianakis, Stratos; Tzortzatou, Georgia

2003-01-01

An 8.7 year-old boy with cryptorchidism and growth hormone (GH) deficiency due to septooptic dysplasia presented testicular descent related to the commencement of hGH treatment. This case suggests a role for GH in testicular descent.

The influence of age and exercise modality on growth hormone bioactivity in women.

PubMed

Gordon, Scott E; Kraemer, William J; Looney, David P; Flanagan, Shawn D; Comstock, Brett A; Hymer, Wesley C

2014-01-01

Prior research has indicated that the loss of skeletal muscle mass and bone mineral density observed with aging is related to the prominent age-related decline in the concentration of serum growth hormone (GH). However, there is limited data on the effects of aging on GH responses to acute bouts of heavy resistance exercise (HRE) and aerobic exercise (AE). The present investigation examined the effects of a HRE protocol and an AE protocol on immunoreactive GH (IGH) and bioactive GH (BGH) in active young and old women. Older women had a diminished serum IGH response to both the HRE and AE protocols compared to the younger women, however a similar response was not observed in serum BGH. Additionally, the HRE protocol elicited a greater BGH response than the AE protocol exclusively in the younger group. Regardless of exercise mode, aging induces an increase in growth hormone polymerization that specifically results in a loss of serum growth hormone immunoreactivity without a concurrent loss of serum growth hormone bioactivity. The greater BGH response to the HRE protocol found in the younger group can be attributed to an unknown serum factor of molecular weight between 30 and 55kD that either potentiated growth hormone bioactivity in response to HRE or inhibited growth hormone bioactivity in response to AE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plasma growth hormone, insulin, and glucagon responses to arginine infusion in children and adolescents with idiopathic short stature, isolated growth hormone deficiency, panhypopituitarism, and anorexia nervosa.

PubMed

Sizonenko, P C; Rabinovitch, A; Schneider, P; Paunier, L; Wollheim, C B; Zahnd, G

1975-09-01

The effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa. The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P less than 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four- to sixfold increases of plasma GH were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.05). Arginine infusion resulted in two- to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic beta cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa

A study of cell electrophoresis as a means of purifying growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

1983-01-01

Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

Growth hormone replacement normalizes impaired fibrinolysis: new insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency.

PubMed

Miljic, D; Miljic, P; Doknic, M; Pekic, S; Stojanovic, M; Cvijovic, G; Micic, D; Popovic, V

2013-12-01

Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Hospital based, interventional, prospective study. Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p<0.01]. Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013.

Pituitary-adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls.

PubMed

Bloch, M; Schmidt, P J; Su, T P; Tobin, M B; Rubinow, D R

1998-06-15

Premenstrual syndrome (PMS) is a cyclic mood disorder, widely believed, yet not conclusively shown, to be of endocrine etiology. This study examines basal levels of several hormones reported, albeit inconsistently, to differ in women with PMS compared with controls. Subjects (10 PMS patients and 10 controls) had their blood drawn for one full menstrual cycle. Subjects' mood and behavioral symptoms were assessed by daily self-ratings and objective ratings. Plasma was assayed for total and free testosterone (T), beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. No differences were observed between the PMS and control groups for beta-EP, ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma levels with a blunting of the normal periovulatory peak, a finding that may be epiphenomenal to age. This study does not confirm previous reports of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it also fails to replicate a previous observation of high free T levels in women with PMS. These results are not supportive of a primary endocrine abnormality in PMS patients.

[Ghrelin: a gastric hormone at the crossroad between growth and appetite regulation].

PubMed

Labarthe, Alexandra; Tolle, Virginie

2016-01-01

Ghrelin is a 28 amino acid peptide hormone synthesized within the gastrointestinal tract. Initially identified as the endogenous ligand of the GHS-R1a (Growth Hormone Secretagogue Receptor 1a), ghrelin is a powerful stimulator of growth hormone (GH) secretion. At the crossroad between nutrition, growth and long-term energy metabolism, ghrelin also plays a unique role as the first identified gastric hormone increasing appetite and adiposity. However, the role of the ghrelin/GHS-R system in the physiology of growth, feeding behaviour and energy homeostasis needs to be better understood. Utilization of pharmacological tools and complementary animal models with deficiency in preproghrelin, ghrelin-O-acyl-transferase (GOAT - the enzyme that acylates ghrelin -) or GHS-R in situations of chronic undernutrition or high fat diet gives a more precise overview of the role of ghrelin in the pathophysiology of eating and metabolic disorders. © Société de Biologie, 2017.

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

PubMed

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

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.

In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an increase of serum cortisol relative to other adrenal hormones.

PubMed

Atzeni, F; Sarzi-Puttini, P; DePortu, S; Cutolo, M; Carrabba, M; Straub, R H

2008-01-01

In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.

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.

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 deficiency in a patient with mitochondrial disease.

PubMed

Rocha, Vera; Rocha, Dalila; Santos, Helena; Sales Marques, Jorge

2015-09-01

Mitochondrial respiratory chain (MRC) disorders, defined as primary diseases of the oxidative phosphorylation system, are a protean group of metabolic disorders, difficult to diagnose and classify. The diagnosis is complex and requires the integration of information obtained by clinical, laboratory testing, imaging and muscle biopsy. They may be associated with endocrine disorders, including hypothyroidism, diabetes mellitus, hyperinsulinemia and growth hormone (GH) deficiency. We describe a case of five years old male with polymalformative syndrome with a systemic involvement. At 6 months of age, he was sent to metabolic consultation because of facial dysmorphy and short stature. During the investigation it was diagnosed at the boy a growth hormone deficiency and because of his multisystemic involvement, muscle biopsy was carried out and showed reduced activity of complex II (38%) of the mitochondrial respiratory chain. Currently, the boy is under GH therapy with growth in the 5th percentile and coenzime Q10. Mitochondrial biology is one of the fastest growing areas in genetics and medicine. Disturbances in mitochondrial metabolism are now known to play a role not only in rare childhood diseases, but also in many common diseases of aging. In mitochondrial disorders, short stature is a common symptom, but its underlying lesion, growth hormone deficiency, is rarely investigated.

Late pubertal growth spurt in a girl with growth hormone deficiency: Is Kaufmann therapy effective in a girl with short stature who responds poorly to growth hormone therapy and estrogen-replacement therapy?

PubMed

Yasuda, Katsuhiko

2017-05-01

A Japanese senior high school girl aged 18 years and 5 months with growth hormone deficiency was referred for primary amenorrhea. Her height was 1.36 m, and her bodyweight was 23.5 kg. She had received daily growth hormone therapy from the age of 5 years. Growth hormone therapy was discontinued at the age of 16 years and 11 months, and estrogen-replacement therapy (ERT) was started to stimulate secondary sexual characteristics. Although ERT was performed until the age of 18 years and 11 months, genital bleeding did not occur. ERT was changed to Kaufmann therapy, and the first genital bleeding occurred 1 year and 4 months later. Finally, regular medically induced menses occurred at the age of 21 years and 10 months. Her height increased by 9 cm in 1 year after the initiation of menstrual bleeding. Kaufmann therapy was associated not only with menstrual bleeding but also with growth spurt. © 2017 Japan Society of Obstetrics and Gynecology.

Mutations in PROP1 cause familial combined pituitary hormone deficiency.

PubMed

Wu, W; Cogan, J D; Pfäffle, R W; Dasen, J S; Frisch, H; O'Connell, S M; Flynn, S E; Brown, M R; Mullis, P E; Parks, J S; Phillips, J A; Rosenfeld, M G

1998-02-01

Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH) and one or more of the other five anterior pituitary hormones. Mutations of the pituitary transcription factor gene POU1F1 (the human homologue of mouse Pit1) are responsible for deficiencies of GH, prolactin and thyroid stimulating hormone (TSH) in Snell and Jackson dwarf mice and in man, while the production of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) is preserved. The Ames dwarf (df) mouse displays a similar phenotype, and appears to be epistatic to Snell and Jackson dwarfism. We have recently positionally cloned the putative Ames dwarf gene Prop1, which encodes a paired-like homeodomain protein that is expressed specifically in embryonic pituitary and is necessary for Pit1 expression. In this report, we have identified four CPHD families with homozygosity or compound heterozygosity for inactivating mutations of PROP1. These mutations in the human PROP1 gene result in a gene product with reduced DNA-binding and transcriptional activation ability in comparison to the product of the murine df mutation. In contrast to individuals with POU1F1 mutations, those with PROP1 mutations cannot produce LH and FSH at a sufficient level and do not enter puberty spontaneously. Our results identify a major cause of CPHD in humans and suggest a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

Corticotropin (ACTH) regulates alternative RNA splicing in Y1 mouse adrenocortical tumor cells.

PubMed

Schimmer, Bernard P; Cordova, Martha

2015-06-15

The stimulatory effect of ACTH on gene expression is well documented and is thought to be a major mechanism by which ACTH maintains the functional and structural integrity of the gland. Previously, we showed that ACTH regulates the accumulation of over 1200 transcripts in Y1 adrenal cells, including a cluster with functions in alternative splicing of RNA. On this basis, we postulated that some of the effects of ACTH on the transcription landscape of Y1 cells are mediated by alternative splicing. In this study, we demonstrate that ACTH regulates the alternative splicing of four transcripts - Gnas, Cd151, Dab2 and Tia1. Inasmuch as alternative splicing potentially affects transcripts from more than two-thirds of the mouse genome, we suggest that these findings are representative of a genome-wide effect of ACTH that impacts on the mRNA and protein composition of the adrenal cortex. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Improved growth velocity of a patient with Noonan-like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low-dose growth hormone therapy.

PubMed

Takasawa, Kei; Takishima, Shigeru; Morioka, Chikako; Nishioka, Masato; Ohashi, Hirofumi; Aoki, Yoko; Shimohira, Masayuki; Kashimada, Kenichi; Morio, Tomohiro

2015-10-01

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: -2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH. © 2015 Wiley Periodicals, Inc.

Thyroid, cortisol and growth hormone levels in adult Nigerians with metabolic syndrome.

PubMed

Udenze, Ifeoma Christiana; Olowoselu, Olusola Festus; Egbuagha, Ephraim Uchenna; Oshodi, Temitope Adewunmi

2017-01-01

The similarities in presentation of cortisol excess, growth hormone deficiency, hypothyroidism and metabolic syndrome suggest that subtle abnormalities of these endocrine hormones may play a causal role in the development of metabolic syndrome. The aim of this study is to determine the levels of cortisol, thyroid and growth hormones in adult Nigerians with metabolic syndrome and determine the relationship between levels of these hormones and components of the syndrome. This was a case control study conducted at the Lagos University Teaching Hospital, Lagos, Nigeria. Participants were fifty adult men and women with the metabolic syndrome, and fifty, age and sex matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the NCEP-ATPIII criteria. Written Informed consent was obtained from the participants. Socio demographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an over-night fast. The Ethics committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the Student's t test. Correlation analysis was employed to determine the associations between variables. Statistical significance was set at P<0.05. Triiodotyronine (T3) was significantly decreased (p<0.001) and thyroxine (T4 ) significantly increased ( p<0.001) in metabolic syndrome compared to healthy controls. T3 correlated positively and significantly with waist circumference (p=0.004), glucose (p= 0.002), total cholesterol ( p=0.001) and LDL- cholesterol ( p<0.001 ) and negatively with body mass index ( p<0.001 )and triglyceride ( p=0.026). T4 had a negative significant correlation with waist circumference (p=0.004). Cortisol and growth hormone levels were similar in metabolic syndrome and controls. Cortisol however had a positive significant correlation with waist/hip ratio (p<0.001) while growth hormone correlated positively with

Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone.

PubMed

Fleseriu, Maria; Findling, James W; Koch, Christian A; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

2014-10-01

Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Mifepristone (300-1200 mg) was administered once daily. ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.

Growth in children with chronic kidney disease: role of nutrition, growth hormone, dialysis, and steroids.

PubMed

Ingulli, Elizabeth G; Mak, Robert H

2014-04-01

Children with chronic kidney disease (CKD) have impaired growth that leads to short stature in adulthood. The problem persists even with successful transplantation and steroid withdrawal protocols. The aim of this review is to provide an overview of the pressing issues related to growth failure in children with CKD both before and after transplantation. Although great strides have been made in dialysis and transplantation, the incidence of abnormal adult height in children growing up with CKD remains as high as 45-60%. The lack of catch-up growth and resultant short stature is a critical issue for self-esteem and quality of life in many children with CKD. Aggressive daily dialysis, improved nutrition, treatment of metabolic bone disease, and the use of recombinant human growth hormone provide some hope for catch-up growth in select patients. The causes of growth failure in the setting of CKD are multifactorial. Attention to all the details by optimizing nutritional, bone and mineral metabolism, correcting metabolic acidosis and anemia, achieving excellent blood pressure control, reversing cardiovascular complications such as left ventricular hypertrophy, and minimizing the use of corticosteroids is the current standard of care. Aggressive daily dialysis can reverse many of the uremic derangements. For patients not yet on dialysis or for those after renal transplant, early institution of recombinant human growth hormone can promote growth. Improved understanding of the mechanisms of hormone resistance may offer novel targets or measurements of treatment effectiveness.

Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat.

PubMed

Obál, F; Payne, L; Kapás, L; Opp, M; Krueger, J M

1991-08-23

To study the possible involvement of hypothalamic growth hormone-releasing factor (GRF) in sleep regulation, a competitive GRF-antagonist, the peptide (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2, was intracerebroventricularly injected into rats (0.003, 0.3, and 14 nmol), and the EEG and brain temperature were recorded for 12 h during the light cycle of the day. Growth hormone (GH) concentrations were determined from plasma samples taken at 20-min intervals for 3 h after 14 nmol GRF-antagonist. The onset of non-rapid eye movement sleep (NREMS) was delayed in response to 0.3 and 14 nmol GRF-antagonist, the duration of NREMS was decreased for one or more hours and after 14 nmol EEG slow wave amplitudes were decreased during NREMS in postinjection hour 1. The high dose of GRF-antagonist also suppressed REMS for 4 h, inhibited GH secretion, and elicited a slight biphasic variation in brain temperature. These findings, together with previous observations indicating a sleep-promoting effect for GRF, support the hypothesis that hypothalamic GRF is involved in sleep regulation and might be responsible for the correlation between NREMS and GH secretion reported in various species.

Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

PubMed Central

Sun, Liou Y; Spong, Adam; Swindell, William R; Fang, Yimin; Hill, Cristal; Huber, Joshua A; Boehm, Jacob D; Westbrook, Reyhan; Salvatori, Roberto; Bartke, Andrzej

2013-01-01

We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity. DOI: http://dx.doi.org/10.7554/eLife.01098.001 PMID:24175087

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

PubMed

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

2015-08-01

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

NASA Technical Reports Server (NTRS)

Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

1992-01-01

Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

Growth hormone and nutrition as protective agents against methotrexate induced enteritis.

PubMed

Ortega, M; de Segura, I A; Vázquez, I; López, J M; De Miguel, E

2001-03-01

To determine whether exogenously administered growth hormone can reduce or prevent chemotherapy-induced intestinal mucosa injury. The expected results will allow to consider its potential clinical use. Experimental and randomized study. Experimental Surgery Service, La Paz University Hospital. Adult Wistar rats weighing 250-300 g. A chemotherapy protocol with methotrexate (MTX) (120 mg/kg) was employed. Animals fed either with a normoproteic or a hyperproteic liquid diet were treated with either saline or growth hormone (1 mg/kg/day) since three days before until four days after chemotherapy. Animals were sacrificed seven days after MTX administration for tissue sampling. Co-administration of growth hormone and a hyperproteic diet increased intestinal crypt proliferation and reduced MTX-induced apoptosis. Jejunal mucosal structure (morphometry), proliferation (Ki-67) and apoptosis (TUNNEL) were assessed.

Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

PubMed

Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

2012-01-01

The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

Hormones in the immune system and their possible role. A critical review.

PubMed

Csaba, György

2014-09-01

Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation.

PubMed Central

Papadimitriou, A; Urena, M; Hamill, G; Stanhope, R; Leiper, A D

1991-01-01

Growth hormone was given to 13 children (nine boys, four girls) with acute leukaemia who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation. Mean age at total body irradiation and bone marrow transplantation was 9.0 years (range 3.7-15.8). Endocrinological investigation was carried out at a mean of 2.0 years (range 0.4-4.0) after bone marrow transplantation. Peak serum growth hormone responses to hypoglycaemia were less than 10.0 micrograms/l (less than 20.0 mU/l) in 10, 10.5 micrograms/l (21.0 mU/l) in one, greater than 16.0 micrograms/l (greater than 32.0 mU/l) in two patients. Mean age of the patients at the start of growth hormone treatment was 12.2 years (range 5.8-18.2). The mean time between total body irradiation and bone marrow transplantation and the start of growth hormone treatment was 3.2 years (range, 1.1-5.0). Height velocity SD score (SD) increased from a mean pretreatment value of -1.27 (0.65) to + 0.22 (0.81) in the first year, +0.16 (1.11) in the second year, and +0.42 (0.71) in the third year of treatment. Height SD score (SD) changed only slightly from -1.52 (0.42) to -1.50 (0.47) in the first year, to -1.50 (0.46) in the second year, and -1.74 (0.92) in the third year. Measurement of segmental proportions showed no significant increase in subischial leg length from -0.87 (0.67) to -0.63 (0.65) in the first year, to -0.58 (0.70) in the second year, and -0.80 (1.14) in the third year of treatment. Our data indicate that children who have undergone total body irradiation and bone marrow transplantation respond to treatment with growth hormone in either of two dose regimens, with an increase in height velocity that is adequate to restore a normal growth rate but not to 'catch up', and that total body irradiation impairs not only spinal but also leg growth, possibly by a direct effect of irradiation on the epiphyses and soft tissues. PMID:2053788

Ethylene and Hormonal Cross Talk in Vegetative Growth and Development1

PubMed Central

Van de Poel, Bram; Smet, Dajo; Van Der Straeten, Dominique

2015-01-01

Ethylene is a gaseous plant hormone that most likely became a functional hormone during the evolution of charophyte green algae, prior to land colonization. From this ancient origin, ethylene evolved into an important growth regulator that is essential for myriad plant developmental processes. In vegetative growth, ethylene appears to have a dual role, stimulating and inhibiting growth, depending on the species, tissue, and cell type, developmental stage, hormonal status, and environmental conditions. Moreover, ethylene signaling and response are part of an intricate network in cross talk with internal and external cues. Besides being a crucial factor in the growth control of roots and shoots, ethylene can promote flowering, fruit ripening and abscission, as well as leaf and petal senescence and abscission and, hence, plays a role in virtually every phase of plant life. Last but not least, together with jasmonates, salicylate, and abscisic acid, ethylene is important in steering stress responses. PMID:26232489

Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism.

PubMed Central

Amselem, S; Sobrier, M L; Duquesnoy, P; Rappaport, R; Postel-Vinay, M C; Gourmelen, M; Dallapiccola, B; Goossens, M

1991-01-01

In addition to its classical effects on growth, growth hormone (GH) has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues. Purification of a rabbit liver protein via its ability to bind GH has allowed the isolation of a cDNA encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors. We have previously shown that this putative growth hormone receptor gene is genetically linked to Laron dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH. Nevertheless, the inability to express the corresponding full-length coding sequence and the lack of a test for growth-promoting function have hampered a direct confirmation of its role in growth. We have now identified three nonsense mutations within this growth hormone receptor gene, lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule, thereby deleting a large portion of both the GH binding domain and the full transmembrane and intracellular domains. Three independent patients with Laron dwarfism born of consanguineous parents were homozygous for these defects. Two defects were identical and consisted of a CG to TG transition. Not only do these results confirm the growth-promoting activity of this receptor but they also suggest that CpG doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism. Images PMID:1999489

Developmental programming: the role of growth hormone.

PubMed

Oberbauer, Anita M

2015-01-01

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1979-01-01

Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

PubMed

Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

2005-01-01

Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.

Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.

PubMed

Kraemer, William J; Ratamess, Nicholas A; Nindl, Bradley C

2017-03-01

The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process. Copyright © 2017 the American Physiological Society.

Reference curve for the first-year growth response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency: validation of the KIGS first-year growth response curve using the Belgian Register for the Study of Growth and Puberty Problems.

PubMed

Straetemans, Saartje; Roelants, Mathieu; Thomas, Muriel; Rooman, Raoul; De Schepper, Jean

2014-01-01

Comparing observed and expected growth after first-year growth hormone (GH) therapy is useful for identifying a poor growth response to GH. To generate a first-year, age-specific growth response reference curve for prepubertal Belgian children with idiopathic growth hormone deficiency (iGHD) treated with a standard weight-adjusted GH dose and to compare this national reference with the response references derived from KIGS. First-year height data of 357 prepubertal children (240 males) with iGHD were analyzed. Smooth reference curves of first-year height velocity (HV) in relation to age were created. Differences with the KIGS targets were evaluated after z-score transformation. The observed first-year HVs were log-normal distributed by age and decreased significantly with age (p<0.001). No GH dose or gender effect was observed (p=0.5). Distance to target height, severity of GHD and occurrence of multiple pituitary hormone deficiencies had a positive effect (p<0.01) on the calculated HV SDS. When applying the KIGS targets for severe iGHD, mean HV SDS was close to zero (-0.09±0.84). The developed age-specific growth response curves enable rapid identification of poor response to first-year GH treatment in prepubertal iGHD children. Our results validate the published growth targets derived from the KIGS database. © 2014 S. Karger AG, Basel.

Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 3; Plasma Analysis Hormone Measurements

NASA Technical Reports Server (NTRS)

Grindeland, R. E.; Popova, I. A.; Grossman, E.; Rudolph, I.

1994-01-01

Plasma from space flight and tail suspended rats was analyzed for a number of constituents in order to evaluate their metabolic status and endocrine function. The data presented here cover plasma hormone measurements. Corticosterone, thyroxine, and testosterone were measured by radioimmunoassay. Prolactin and growth hormone were measured by double antibody immunoassays using hormones and antisera prepared in house. Data were evaluated by analysis of variance.

Influence of growth hormone replacement on neurological and psychomotor development. Case report.

PubMed

Motta, Felipe; Eisencraft, Adriana Pasmanik; Crisostomo, Lindiane Gomes

2018-05-14

The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score -6.89), low growth rate, and low weight (z-score -7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children - for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.

Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment.

PubMed

Vuralli, Dogus; Gonc, E Nazli; Ozon, Z Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

2017-06-01

We aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Two hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. Sixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. Early reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or 'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development. Copyright © 2017. Published by Elsevier Ltd.

Cognitive and Adaptive Advantages of Growth Hormone Treatment in Children with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Dykens, Elisabeth M.; Roof, Elizabeth; Hunt-Hawkins, Hailee

2017-01-01

Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient…

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists.

PubMed

Jaszberenyi, Miklos; Rick, Ferenc G; Popovics, Petra; Block, Norman L; Zarandi, Marta; Cai, Ren-Zhi; Vidaurre, Irving; Szalontay, Luca; Jayakumar, Arumugam R; Schally, Andrew V

2014-01-14

The dismal prognosis of malignant brain tumors drives the development of new treatment modalities. In view of the multiple activities of growth hormone-releasing hormone (GHRH), we hypothesized that pretreatment with a GHRH agonist, JI-34, might increase the susceptibility of U-87 MG glioblastoma multiforme (GBM) cells to subsequent treatment with the cytotoxic drug, doxorubicin (DOX). This concept was corroborated by our findings, in vivo, showing that the combination of the GHRH agonist, JI-34, and DOX inhibited the growth of GBM tumors, transplanted into nude mice, more than DOX alone. In vitro, the pretreatment of GBM cells with JI-34 potentiated inhibitory effects of DOX on cell proliferation, diminished cell size and viability, and promoted apoptotic processes, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay, ApoLive-Glo multiplex assay, and cell volumetric assay. Proteomic studies further revealed that the pretreatment with GHRH agonist evoked differentiation decreasing the expression of the neuroectodermal stem cell antigen, nestin, and up-regulating the glial maturation marker, GFAP. The GHRH agonist also reduced the release of humoral regulators of glial growth, such as FGF basic and TGFβ. Proteomic and gene-expression (RT-PCR) studies confirmed the strong proapoptotic activity (increase in p53, decrease in v-myc and Bcl-2) and anti-invasive potential (decrease in integrin α3) of the combination of GHRH agonist and DOX. These findings indicate that the GHRH agonists can potentiate the anticancer activity of the traditional chemotherapeutic drug, DOX, by multiple mechanisms including the induction of differentiation of cancer cells.

In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

PubMed

Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2008-03-01

In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

DTIC Science & Technology

2011-09-30

massey.ac.nz Award Number: N000141110434 LONG-TERM GOALS Physiological indicators of stress in wild marine mammals, the interrelationships between...hormones (GC), aldosterone (A), thyroid hormones (TH), and catecholamines within a free-ranging northern elephant seal population and its...additional individuals per year). Serum samples will be processed for ACTH, cortisol, aldosterone , catecholamines (epinephrine, norepinephrine), and

Purification and cultivation of human pituitary growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Hymer, W. C.

1978-01-01

The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

[Effects of synthetic neuropeptides in psycho-organic brain syndrome. Results with ACTH4-10 and ACTH4-9-analog (author's transl)].

PubMed

Schneider, E; Jacobi, P; van Riezen, H; Voerman, J W; Fischer, P A

1981-09-01

The effects of ACTH4-10 (Org O163) and of the ACTH4-9 analog (Org 2766) were tested in 20 male patients suffering from a mild to moderate cerebroorganic impairment. Patients were aged between 51-72 years (mean 60.9). Org 2766 was given in dosages of 0.05 mg, 0.5 mg and 5 mg, Org O163 in a dosage of 30 mg. The investigation was based on a randomized incomplete crossover design. By means of psychological tests the effects of the synthetic neuropeptides on memory, state of well-being, attention, vigilance and psychomotor function were investigated. The statistical analysis of the results did not reveal any effects of both substances on the functions tested. These results are in agreement with those of other studies in man using similar methods and acute administration of ACTH4-10 and/or Org 2766. In such studies only effects of reactive inhibition of attention and motivation could be demonstrated consistently.

Changes in Plasma ACTH Levels and Corticotroph Tumor Size in Patients With Cushing's Disease During Long-term Treatment With the Glucocorticoid Receptor Antagonist Mifepristone

PubMed Central

Findling, James W.; Koch, Christian A.; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman

2014-01-01

Context: Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Objective: Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. Design and Setting: The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Patients: Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Interventions: Mifepristone (300–1200 mg) was administered once daily. Main Outcome Measures: ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. Results: A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. Conclusions: In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth. PMID:25013998

Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

PubMed

Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

2016-04-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones

PubMed Central

Stephens, Mary Ann C.; Mahon, Pamela B.; McCaul, Mary E.; Wand, Gary S.

2016-01-01

Summary Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to

[Quality of life of young adults after a growth hormone therapy with childhood onset].

PubMed

Quitmann, J H; Rohenkohl, A C; Kammerer, U; Schöfl, C; Bullinger, M; Dörr, H-G

2014-11-01

Little is known about the health-related quality of life of young adults with childhood onset idiopathic growth hormone deficiency or neurosecretory dysfunction of growth hormone secretion, who have been treated with recombinant human growth hormone (GH). Patients were diagnosed and treated with human growth hormone at the University Children´s Hospital in Erlangen (n=85). The data of both groups were merged for analysis, because no difference between idiopathic growth hormone deficiency and neurosecretory dysfunction of growth hormone secretion in auxological. Data were found. Health-related quality of life was cross- sectionally assessed after the end of growth hormone therapy with the Short Form-36 Health Survey and the Nottingham Health Profiles for which population based norm data are available. At the time of the survey, the patients (53 m, 32 f) were 23.5 ± 4.6 years old. At start of GH therapy, age was 10.5 ± 2.8 and at the end 16.3 ± 1,4 years. At start, height SDS was -3.20 ± 1.06. GH dose was 0,026 ± 0,012 mg/kg/d (daily s. c.-injections). The increase in height SDS after the end of GH therapy was 1.69 ± 1.22.  Compared to the reference population, patients reported significantly lower scores on the scales energy level, vitality, social functioning, indicating a greater social isolation, a stronger emotional reaction, an increased loss of mobility and a worse psychological state. Young adults report specific impairments after completion of GH therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

PubMed

Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

2015-09-01

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

PubMed

Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.

PubMed

Bomback, Andrew S; Canetta, Pietro A; Beck, Laurence H; Ayalon, Rivka; Radhakrishnan, Jai; Appel, Gerald B

2012-01-01

Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to <0.5 g/g (complete remission) or 0.5-3.5 g/g (partial remission). The study included 5 subjects with resistant idiopathic MN, 5 subjects with resistant MCD (n = 2)/FSGS (n = 3), and 5 subjects with resistant IgA nephropathy. Two resistant MN subjects achieved partial remission on ACTH therapy, although 3 achieved immunologic remission of disease (PLA(2)R antibody disappeared by 4 months of therapy). One subject with resistant FSGS achieved complete remission on ACTH; one subject with resistant MCD achieved partial remission but relapsed within 4 weeks of stopping ACTH. Two subjects with resistant IgA nephropathy demonstrated >50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease. Copyright © 2012 S. Karger AG, Basel.

A longitudinal study of craniofacial growth in idiopathic short stature and growth hormone-deficient boys treated with growth hormone.

PubMed

Kjellberg, H; Wikland, K Albertsson

2007-06-01

The aim of this prospective, longitudinal, controlled study is to describe the long-term safety and efficacy of growth hormone (GH) administration on craniofacial morphology in boys with short stature. Forty-six boys, who started GH treatment at the Department of Paediatrics Göteborg Paediatric Growth Research Centre, were consecutively included in the study. Twenty-five boys were classified as growth hormone-deficient (GHD) and 21 as idiopathic short stature (ISS). The patients were injected with 33 (n=31) or 67 (n=15) microg GH/kg body weight/day. The mean age at the start of treatment was 11.8 years [standard deviation (SD) 1.7]. To assess craniofacial growth, standard lateral cephalometric radiographs were obtained at the start of GH treatment, annually during 4 years, and at the end of GH treatment or when growth was less than 1 cm/year. The mean follow-up period was 6.4 years (SD 1.4). Growth changes were compared with boys from a semi-longitudinal reference group of 130 healthy subjects, 7-21 years of age. t-tests for independent and paired samples and multiple regression analysis were applied. Age- and gender-specific standard deviation scores for the cephalometric variables were calculated. Repeated measures analysis of variance was used to identify significant covariates over time, such as low/high GH dose and GHD/ISS and orthodontic treatment. During the study period, eight (out of 40) boys were treated with fixed orthodontic appliances, three with functional appliances (activators), and three with other appliances (plates and lingual arches). During GH treatment period, an overall enhancement in growth of the facial skeleton was observed in boys with short stature. The changes induced by GH yielded a more prognathic growth pattern, a more anterior position of the jaws in relation to the cranial base, and increased anterior rotation of the mandible. The mandibular corpus length and anterior face height of the GH-treated boys were greater at the end of

Levels of hormones and cytokines associated with growth in Honamlı and native hair goats.

PubMed

Devrim, A K; Elmaz, O; Mamak, N; Sudagidan, M

2015-01-01

This study was designed to assess alterations of hormone and cytokine levels associated with growth period during puberty in Honamlı goats which were identified as a new goat breed and had one of the highest meat production potential among the other goat breeds in Turkey. Honamlı goats are originated from native hair goats, so parallel studies of sampling and analyzing were conducted also in native hair goats which have moderate meat production. Blood serum samples of Honamlı (n=90) and native hair goats (n=90) were obtained from the pure herds in Korkuteli and Ka districts of Anatolia. Concentrations of growth hormone (GH), myostatin (MSTN), insulin-like growth factor (IGF), growth hormone releasing hormone (GHRH), growth hormone releasing peptide (GHRP), leptin, transforming growth factor-betal (TGF-β1) and vascular endothelial cell growth factor (VEGF) levels were measured by ELISA in each breed in the age groups of 4, 8 and 12 months. The present results indicate interesting correlations among the age groups and all the examined hormone and cytokine parameters exhibited significant (P<0.05 and P<0.001) differences. The parameters investigated were usually begun to increase after 4 months of age in the both breeds and sexes. Therefore, this paper supported the view that the beginning of hormonal alterations of goats could occur at 4th month of age. The results reported here emphasize the primary role played by GH, MSTN, IGF-1, leptin, GHRH, GHRP, TGF-βi and VEGF in the first year growth period of goats.

Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth, and development.

PubMed

Mahajan, Muktar A; Samuels, Herbert H

2005-06-01

Nuclear hormone receptor coregulator (NRC) (also referred to as activating signal cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator activating receptor-interacting protein, and 250-kDa receptor associated protein) belongs to a growing class of nuclear cofactors widely known as coregulators or coactivators that are necessary for transcriptional activation of target genes. The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal activation domain (AD1) and a second more centrally located activation domain (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif (LxxLL-2) located in the C-terminal region of NRC is more restricted in its nuclear hormone receptor specificity. The intrinsic activation potential of NRC is regulated by a C-terminal serine, threonine, leucine-regulatory domain. The potential role of NRC as a cointegrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known transcriptional regulators including CBP/p300. Recent studies in mice indicate that deletion of both NRC alleles leads to embryonic lethality resulting from general growth retardation coupled with developmental defects in the heart, liver, brain, and placenta. NRC(-/-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6 NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing.

Epistatic effects between pairs of the growth hormone secretagogue receptor 1a, growth hormone, growth hormone receptor, non-SMC condensin I complex, subunit G and stearoyl-CoA desaturase genes on carcass, price-related and fatty acid composition traits in Japanese Black cattle.

PubMed

Komatsu, Masanori; Nishino, Kagetomo; Fujimori, Yuki; Haga, Yasutoshi; Iwama, Nagako; Arakawa, Aisaku; Aihara, Yoshito; Takeda, Hisato; Takahashi, Hideaki

2018-02-01

Growth hormone secretagogue receptor 1a (GHSR1a), growth hormone (GH), growth hormone receptor (GHR), non-SMC condensin I complex, subunit G (NCAPG) and stearoyl-CoA desaturase (SCD), are known to play important roles in growth and lipid metabolisms. Single and epistatic effects of the five genes on carcass, price-related and fatty acid (FA) composition traits were analyzed in a commercial Japanese Black cattle population of Ibaraki Prefecture. A total of 650 steers and 116 heifers for carcass and price-related traits, and 158 steers for FA composition traits were used in this study. Epistatic effects between pairs of the five genes were found in several traits. Alleles showing strain-specific differences in the five genes had significant single and epistatic effects in some traits. The data suggest that a TG-repeat polymorphism of the GHSR1a.5'UTR-(TG) n locus plays a central role in gene-gene epistatic interaction of FA composition traits in the adipose tissue of Japanese Black cattle. © 2017 Japanese Society of Animal Science.

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.

PubMed

Milosević, Verica Lj; Stevanović, Darko M; Nesić, Dejan M; Sosić-Jurjević, Branka T; Ajdzanović, Vladimir Z; Starcević, Vesna P; Severs, Walter B

2010-06-01

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.

[Growth hormone: a magical potion?].

PubMed

Schlienger, J L; Goichot, B

1998-04-01

The various components of the growth hormone (GH)-insulin-like growth factor (IGF-I) axis and their binding proteins have many peripheral effects, mainly on bone, growth, activation of main cellular functions, energy metabolism and protein anabolism. They contribute to adapt an individual to circumstances of life and illness. The unlimited supply of recombinant GH makes it possible to treat not only children with short stature but other disorders. In adults with GH deficiency, it has a marked effect on subjective well-being and body composition, and improves physical activity. GH may be promoted in new therapeutic areas such as severe hypercatabolic and denutrition states, dilated cardiomyopathy and several other more hypothetical areas. GH is not a wonder drug increasing physical performances in sport competitors or fighting against senescence. GH is a new therapeutic tool. Its efficacy must be evaluated through double-blind, placebo-controlled clinical trials. Currently, only benefits on psychological and physical symptoms of GH deficiency in adults have been validated.

Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

PubMed

Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

2015-01-01

Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Genetics Home Reference: isolated growth hormone deficiency

MedlinePlus

... hormone deficiency type III Patient Support and Advocacy Resources (3 links) Human Growth Foundation Little People UK The MAGIC Foundation ... Reviewed : February 2012 Published : June 26, 2018 The resources on this site should not be used as a substitute ... Department of Health & Human Services National Institutes of Health National Library of ...

Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

PubMed

Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E

2012-11-15

To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.

Response to the high-dose corticotrophin stimulation test depends on plasma adrenocotropin hormone levels in septic shock.

PubMed

Llompart-Pou, Juan Antonio; Raurich, Joan Maria; Ayestarán, Ignacio; Fernández-de-Castillo, Ana G; Pérez-Bárcena, Jon; Ibáñez, Jordi

2012-06-01

The use of the high-dose corticotrophin stimulation test (HDCST) as a guide to use low-dose steroid therapy in septic shock is controversial. The adrenocotropin hormone (ACTH) constitutes the immediate stimuli to produce cortisol. We evaluated the correlation of the response to the HDCST with plasma ACTH levels in patients with septic shock. This is a retrospective review of 102 patients with septic shock in which adrenal function was evaluated using the HDCST and plasma ACTH levels were measured. Patients with a δ cortisol of 9 μg/dL or less were considered as nonresponders or with subnormal response. The association between plasma ACTH levels and the response to the HDCST was investigated. Sixty-four patients (62.7%) had a subnormal response. Plasma ACTH levels were higher in patients with subnormal response (19.8 [11.7-31.4] vs 10.0 [7.0-21.2] pg/mL; P = .002). Patients in the highest quartile of plasma ACTH had lower δ cortisol (P = .014) and higher percentage of subnormal response (P = .005). The optimal cutoff point of plasma ACTH level with fewest false classifications was 10 pg/mL (sensitivity, 0.83 [95% confidence interval, 074-0.90] and specificity, 0.50 [95% confidence interval, 0.74-0.90]). Patients with septic shock with higher plasma ACTH values presented a subnormal response to the HDCST. The number of patients who failed to the HDCST was higher as plasma ACTH increased. Copyright © 2012 Elsevier Inc. All rights reserved.

Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

PubMed

Noel, G L; Dimond, R C; Earll, J M; Frantz, A G

1976-05-01

Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency.

PubMed

Lutfallah, Chantal; Wang, Weihua; Mason, J Ian; Chang, Ying Tai; Haider, Anzar; Rich, Barry; Castro-Magana, Mariano; Copeland, Kenneth C; David, Raphael; Pang, Songya

2002-06-01

To define the hormonal criteria via genotypic proof for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency in the adrenals and gonads, we investigated the type II 3beta-HSD genotype in 55 patients with clinical and/or hormonal presentation suggesting compromised adrenal with or without gonadal 3beta-HSD activity. Fourteen patients (11 males and 3 females) had ambiguous genitalia with or without salt wasting and with or without premature pubarche. One female neonate had salt wasting only. Twenty-five children (4 males and 21 females) had premature pubarche only. Fifteen adolescent and adult females had hirsutism with or without menstrual disorder. The type II 3beta-HSD gene, including the promoter region up to -1053 base, all exons I, II, III, IV, and exon and intron boundaries, was sequenced in all subjects. Eight patients had a proven or predictably deleterious mutation in both alleles of the type II 3beta-HSD gene, and 47 patients had no apparent mutation in the gene. ACTH-stimulated (1 h post iv bolus of 250 microg Cortrosyn) serum 17-hydroxypregnenolone (Delta5-17P) levels and basal and ACTH-stimulated ratios of Delta5-17P to cortisol (F) in the genotypic proven patients were unequivocally higher than those of age-matched or pubic hair stage matched genotype-normal patients or control subjects (n = 7-30 for each group). All other baseline and ACTH-stimulated hormone parameters, including dehydroepiandrosterone (DHEA) levels, ratios of Delta5-17P to 17-OHP and DHEA to androstenedione in the genotype-proven patients, overlapped with the genotype-normal patients or control subjects. The hormonal findings in the genotype-proven patients suggest that the following hormonal criteria are compatible with 3beta-HSD deficiency congenital adrenal hyperplasia (numeric and graphic reference standards from infancy to adulthood are provided): ACTH-stimulated Delta5-17P levels in 1) neonatal infants with ambiguous genitalia at or greater than 378 nmol/liter equivalent

Effects of glucose infusion on neuroendocrine and cognitive parameters in Addison disease.

PubMed

Klement, Johanna; Hubold, Christian; Hallschmid, Manfred; Loeck, Cecilia; Oltmanns, Kerstin M; Lehnert, Hendrik; Born, Jan; Peters, Achim

2009-12-01

Sucrose intake has been shown to suppress increased adrenocorticotropic hormone (ACTH) levels in adrenalectomized rats, suggesting that increased cerebral energy supply can compensate for the loss of glucocorticoid feedback inhibition of the hypothalamo-pituitary-adrenal axis. We hypothesized that glucose infusion might acutely down-regulate increased ACTH secretion in patients with Addison disease. We studied 8 patients with primary adrenal insufficiency (Addison group) with short-term discontinuation of hydrocortisone substitution and 8 matched healthy controls in 2 randomized conditions. Subjects received either intravenous glucose infusion (0.75 g glucose per kilogram body weight for 2.5 hours) or placebo. Concentrations of ACTH, cortisol, catecholamines, growth hormone, glucagon, and insulin were measured; and cognitive functions as well as neuroglycopenic and autonomic symptoms were assessed. The ACTH concentrations were not affected by glucose infusion either in the Addison or in the control group. Likewise, concentrations of cortisol, epinephrine, norepinephrine, growth hormone, and glucagon remained unchanged in both groups. Neurocognitive performance and symptom scores were likewise not affected. Independent of glucose infusion, attention of the Addison patients was impaired in comparison with the control group. Our study in patients with Addison disease was not able to support the assumption of a compensatory effect of intravenous glucose infusion on hormonal parameters and neurocognitive symptoms in states of chronic cortisol deficiency. Further studies should examine whether different regimens of glucose administration are more effective.

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease.

PubMed

Srinivasan, Lakshmi; Laws, Edward R; Dodd, Robert L; Monita, Monique M; Tannenbaum, Christyn E; Kirkeby, Kjersti M; Chu, Olivia S; Harsh, Griffith R; Katznelson, Laurence

2011-12-01

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25-55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.

Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.

PubMed

Malmlöf, K; Johansen, P B; Haahr, P M; Wilken, M; Oxlund, H

1999-12-01

The present study was undertaken to study the growth hormone-releasing properties and growth-promoting effect of a GH secretagogue ipamorelin (IPA) in rats given the synthetic glucocorticoid methylprednisolone (MP). In a first experiment, rats received either saline or MP (5.0 mg/kg) for 8 days. Treatment with MP significantly (P< 0.001) decreased body weight gain, but the acute response to either IPA or growth hormone releasing hormone (GHRH) in terms of plasma GH was not changed. In a second experiment, venous catheters were surgically implanted. On the next day, rats were randomly allocated to receive saline alone, MP alone (5.0 mg/kg) or MP plus IPA in doses of 0.4 or 1.6 mg/kg/day for 10 days. IPA was administered intravenously four times a day.MP treatment significantly (P< 0.05) retarded recovery from surgery in terms of body weight. Thus, saline treated animals lost 4.0 +/- 3.5 g over the entire experimental period, whereas animals receiving MP lost 13. 6 +/- 2.9 g. When IPA was given together with MP, losses in body weight were significantly (P< 0.05) reduced to 2.3 +/- 2.0 and 1.6 +/- 2.0 g in animals given the high and low dose of IPA, respectively. In parallel with this IGF-I levels increased. In conclusion, this work shows that MP does not disrupt the response of the GH-IGF-I axis to an exogenous stimulus like IPA, and repeated stimulation leads to increases in IGF-I and of body weight gain. Copyright 1999 Harcourt Publishers Ltd.

Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem.

PubMed

Duque-Díaz, Ewing; Díaz-Cabiale, Zaida; Narváez, José Angel; Coveñas, Rafael

2017-03-01

An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review.

PubMed

Deodati, Annalisa; Cianfarani, Stefano

2011-03-11

To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. Systematic review. Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. Three randomised controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.

Growth Hormone Deficiency, Brain Development, and Intelligence

ERIC Educational Resources Information Center

Meyer-Bahlburg, Heino F. L.; And Others

1978-01-01

Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

Hypopituitarism.

PubMed

Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

2016-11-12

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

International Comparison of Adult Height in Children with Growth Hormone Deficiency and Limitations of Growth Hormone Treatment in Japan.

PubMed

Tanaka, Toshiaki

2017-03-01

The approved therapeutic dose of growth hormone (GH) for growth hormone deficiency (GHD) varies depending on the country. Japan has the lowest therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment for GHD is considered as a replacement therapy and in fact, a dose of 0.175 mg/kg/week is slightly higher than GH secretion in prepubertal healthy children but nearly the same as that of pubertal children. Although the same growth rate as that of healthy children is expected in response to replacement therapy, the catch-up growth observed for the first 1 to 2 years of GH treatment was misinterpreted as an effect of the GH replacement therapy. The real effect of the GH replacement therapy was the growth rate appeared after more than 3 years of GH therapy, when patients showed nearly the same growth rate as healthy children. Therefore, children with GHD can have a higher growth rate than healthy children only for the first 1 to 2 years of GH therapy, after which their growth rate begins to wane. In the United States and Europe, the various therapeutic doses and high-dose treatment are accepted and the SD score of adult height after treatment is higher than that in Japan. The improvement degree of the height SD score and the adult height SD score with GH therapy are lower in Japan compared with other countries that administer a similar therapeutic dose. This suggests that the response to GH can be affected by race. Actual comparison of the response to GH between Japanese and Caucasian patients using KIGS (Pharmacia International Growth Database) data showed that both the short-term response and the effect on adult height were reduced in Japanese patients. As there is a strong positive correlation between adult height and height at the onset of puberty, treatment methods that can increase pubertal growth will be considered in the future for patients with GDH who enter puberty with short stature. Copyright© of YS Medical Media ltd.

Prolonged whole body immersion in cold water: hormonal and metabolic changes.

PubMed

Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

1990-03-01

To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

PubMed Central

Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret C S; Casanueva, Felipe F; Chanson, Philippe; Chatelain, Pierre; Choong, Catherine S; Clemmons, David R; Cohen, Laurie E; Cohen, Pinchas; Frystyk, Jan; Grimberg, Adda; Hasegawa, Yukihiro; Haymond, Morey W; Ho, Ken; Holly, Jeff M P; Horikawa, Reiko; Höybye, Charlotte; Jorgensen, Jens Otto L; Johannsson, Gudmundur; Juul, Anders; Katznelson, Laurence; Kopchick, John J; Lee, K O; Lee, Kuk-Wha; Luo, Xiaoping; Melmed, Shlomo; Miller, Bradley S; Misra, Madhusmita; Popovic, Vera; Rosenfeld, Ron G; Ross, Judith; Ross, Richard J; Saenger, Paul; Strasburger, Christian J; Thorner, Michael O; Werner, Haim; Yuen, Kevin

2016-01-01

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. PMID:27009113

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations.

PubMed

Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret C S; Casanueva, Felipe F; Chanson, Philippe; Chatelain, Pierre; Choong, Catherine S; Clemmons, David R; Cohen, Laurie E; Cohen, Pinchas; Frystyk, Jan; Grimberg, Adda; Hasegawa, Yukihiro; Haymond, Morey W; Ho, Ken; Hoffman, Andrew R; Holly, Jeff M P; Horikawa, Reiko; Höybye, Charlotte; Jorgensen, Jens Otto L; Johannsson, Gudmundur; Juul, Anders; Katznelson, Laurence; Kopchick, John J; Lee, K O; Lee, Kuk-Wha; Luo, Xiaoping; Melmed, Shlomo; Miller, Bradley S; Misra, Madhusmita; Popovic, Vera; Rosenfeld, Ron G; Ross, Judith; Ross, Richard J; Saenger, Paul; Strasburger, Christian J; Thorner, Michael O; Werner, Haim; Yuen, Kevin

2016-06-01

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. © 2016 The authors.

Growth Control and Biophoton Radiation by Plant Hormones in Red Bean

NASA Astrophysics Data System (ADS)

Kai, Shoichi; Moriya, Tomoyuki; Fujimoto, Tokio

1995-12-01

The growth kinetics of seeds of red beans ( Phaseolus angularis ) was investigated by externally adding various hormones (gibberellin (GA3)), abscisic acid (ABA) and indole acetic acid (IAA)) during germination. For root growth of red beans, GA3 always acted as an activator while ABA as an inhibitor. IAA was both an activator and an inhibitor depending on its concentration. Root growth could be described by a stochastic logistic equation. The hormone concentration dependences of coefficients of the equation were determined. The hormone influences on biophoton radiation were also investgated. With GA3, the intensity of spontaneous bioluminescence increased with time and showed two strong radiation periods, in which strong localization of bioluminescence was induced. However with ABA and IAA, weaker bioluminescences were observed. The location of the strong radiation induced by GA3 was determined as the growing point near a root cap, by use of a two-dimensional photon counting system.

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

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

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6),more » who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.« less

Lepidium meyenii (Maca) enhances the serum levels of luteinising hormone in female rats.

PubMed

Uchiyama, Fumiaki; Jikyo, Tamaki; Takeda, Ryosuke; Ogata, Misato

2014-02-03

Lepidium meyenii (Maca) is traditionally employed in the Andean region for its supposed fertility benefits. This study investigated the effect of Maca on the serum pituitary hormone levels during the pro-oestrus phase. Maca powder was made from the tubers of Lepidium meyenii Walp collected, dried, and reduced to powder at the plantation in Junín Plateau and was purchased from Yamano del Perú SAC. The Maca powder was identified by chemical profiling and taxonomic methods. Two groups of female Sprague-Dawley rats were provided feed with normal feed containing 5%, 25%, or 50% Maca powder ad libitum for 7 weeks. At 1800h of the proestrus stage, the rats were euthanised, and blood samples were collected for serum isolation. The serum pituitary hormone levels were measured using enzyme-linked immunosorbent assays (ELISAs). No significant differences in feed intake or growth rate were observed among the rats. During the pro-oestrus stage, a 4.5-fold increase (P<0.01) in luteinising hormone (LH) and a 19-fold increase (P<0.01) in follicle-stimulating hormone (FSH) were observed in the sera of rats fed with 50% Maca powder compared with the control rats. No significant differences were observed in the levels of the other pituitary hormones, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH). A dose-dependent increase of LH serum levels was observed within the range of 3-30g Maca/kg. Furthermore, the enhancement of the LH serum levels was specific to the pro-oestrus LH surge. The present study demonstrates that Maca uniquely enhances the LH serum levels of pituitary hormones in female rats during the pro-oestrus LH surge and acts in a pharmacological, dose-dependent manner. These findings support the traditional use of Maca to enhance fertility and suggest a potential molecular mechanism responsible for its effects. © 2013 Elsevier Ireland Ltd. All rights reserved.

The effect of diphenylhydantoin on metabolic and growth hormone changes during and after exercise.

PubMed Central

Chalmers, R J; Johnson, R H

1983-01-01

Metabolic and human growth hormone responses to exercise were investigated in six normal healthy subjects on two occasions with and without an oral dose of diphenylhydantoin (500 mg). Serum diphenylhydantoin concentrations were similar in all subjects and were just below the accepted therapeutic range for epileptic patients. There was no significant difference in blood lactate, pyruvate or glucose concentrations with diphenylhydantoin. Plasma free fatty acids, and blood glycerol and total ketone concentrations were greater after exercise following diphenylhydantoin. Significantly greater concentrations of human growth hormone occurred during exercise with diphenylhydantoin. Further investigation of the mechanisms by which diphenylhydantoin alters lipolysis and human growth hormone release would be of value as these metabolic and hormonal effects could influence exercise tolerance in athletics and other pursuits. PMID:6886706

THE EFFECT OF ADRENAL STEROIDS, CORTICOTROPIN, AND GROWTH HORMONE ON RESISTANCE TO EXPERIMENTAL INFECTIONS

PubMed Central

Kass, Edward H.; Lundgren, Marguerite M.; Finland, Maxwell

1954-01-01

Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

PubMed

Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard

2017-01-01

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Growth hormone and drug metabolism. Acute effects on microsomal mixed-function oxidase activities in rat liver.

PubMed Central

Wilson, J T; Spelsberg, T C

1976-01-01

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases. PMID:938458

Somatotype and stress hormone levels in young soccer players.

PubMed

Handziska, E; Handziski, Z; Gjorgoski, I; Dalip, M

2015-11-01

The relationship between somatotype and cortisol and adrenocorticotropic (ACTH) hormone concentrations at rest or after exercise in adolescent soccer players at different time points throughout a soccer season is not understood. Therefore, the aim of this study was to examine the relationship between somatotype and cortisol and ACTH concentrations at rest and after exercise in adolescent soccer players at different time points during a soccer season. During the first 4 months of the soccer season, 47 soccer players (between 15-17 years of age) were tested at three different time points including at baseline, after 6 weeks, and at the end of 4 months. Testing included anaerobic threshold (AnT, km/h) and maximal speed of running (Max, km/h) were measured with Conconi protocol on treadmill. Before and after a maximal exercise Test, plasma levels of cortisol (ug/dL) and ACTH (pg/ml) were assessed by chemiluminometry enzyme amplificated method. Heath-Carter anthropometric somatotype model was used to determine 13 elements of somatotype. Descriptive statistics and multiple regression were used for statistical analysis (P<0.05). Body composition and AnT were not significantly different between each time point of testing. The mesomorph-ectomorph (N.=21), balanced mesomorph (N.=8) and balanced ectomorph (N.=7) were the most frequent somatotypes. There were significant decrements of cortisol plasma levels (at rest 33.4%; after test 27.46%), with insignificant changes of ACTH plasma levels, after 6 weeks of preparation phase and after finishing of half season, at rest and after maximal treadmill test. There were significant correlation between ACTH levels at rest (R=0.44; P<0.01) and some somatotypes (mesomorph endomorph, central and balanced endomorph) and ACTH levels after maximal exercise test (R=0.36; P<0.05) and balanced ectomorph and endomorph mesomorph. There were significant correlation between cortisol levels after maximal exercise test at the beginning of training

Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

PubMed

Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

2016-07-01

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

A Role for Central Nervous Growth Hormone-Releasing Hormone Signaling in the Consolidation of Declarative Memories

PubMed Central

Michel, Christian; Perras, Boris; Born, Jan

2011-01-01

Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH) on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg) that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05). The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05). Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation. PMID:21850272

Growth Hormone (GH) and Cardiovascular System

PubMed Central

Díaz, Oscar; Devesa, Pablo

2018-01-01

This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases. PMID:29346331

Impaired hair growth and wound healing in mice lacking thyroid hormone receptors.

PubMed

Contreras-Jurado, Constanza; García-Serrano, Laura; Martínez-Fernández, Mónica; Ruiz-Llorente, Lidia; Paramio, Jesus M; Aranda, Ana

2014-01-01