Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women.

Background: Oral administration of estradiol (E2) generally increases GH secretion in postmenopausal women. Oral administration of E2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied.

Effects of Toremifene, a Selective Estrogen Receptor Modulator, on Spontaneous and Stimulated GH Secretion, IGF-I, and IGF-Binding Proteins in Healthy Elderly Subjects.

Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene.

One-year intranasal application of growth hormone releasing peptide-2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient.

Background: In Japan, growth hormone releasing peptide-2 (GHRP-2) is clinically used as a diagnostic agent for growth hormone secretion deficiency, but the therapeutic application of GHRP-2 has not been studied in anorexia nervosa. GHRP-2 reportedly exhibits agonistic action for ghrelin receptor and increases food intake.

Methods: We administered GHRP-2 to a patient with a 20-year history of anorexia nervosa to determine whether GHRP-2 treatment increases food intake and body weight.

Estrogen-like potentiation of ghrelin-stimulated GH secretion by fulvestrant, a putatively selective ER antagonist, in postmenopausal women.

Context: Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause.

Objective And Design: The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion.

Setting: The study was performed at the Mayo Center for Clinical and Translational Science.

Short-term estradiol supplementation potentiates low-dose ghrelin action in the presence of GHRH or somatostatin in older women.

Context: Ghrelin is a potent gastric-derived GH-releasing peptide. How ghrelin interacts with sex steroids, GHRH, and somatostatin (SS) is not known.

Objective: Our objective was to test the hypotheses that ghrelin's interactions with GHRH (synergistic) and SS (disinhibitory) are ghrelin dose-dependent and amplified by estrogen.

Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women.

Objective: Estrogen stimulates pulsatile secretion of GH, via mechanisms that are largely unknown. An untested hypothesis is that estradiol (E₂) drives GH secretion by amplifying interactions among GH-releasing hormone (GHRH), somatostatin (SS), and GH-releasing peptide (GHRP).

Design: The design comprised double-blind randomized prospective administration of transdermal E₂ vs placebo to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions for 13 h overnight with or without continuous GHRP2 stimulation.

Differential pulsatile secretagogue control of GH secretion in healthy men.

Pulsatile growth hormone (GH) secretion putatively reflects integrated regulation by GH-releasing hormone (GHRH), somatostatin (SST), and GH-releasing peptide (GHRP). GHRH and SST secretion is itself pulsatile. However, how GHRH and SST pulses act along with GHRP to jointly determine pulsatile GH secretion is unclear.

Sex steroids, GHRH, somatostatin, IGF-I, and IGFBP-1 modulate ghrelin's dose-dependent drive of pulsatile GH secretion in healthy older men.

Context: Ghrelin is a potent endogenous stimulator of GH secretion. However, clinical factors that regulate ghrelin dose-responsiveness are incompletely defined.

Objective: The aim of the study was to test the multipathway hypothesis that testosterone (T) and estradiol, GHRH, and somatostatin (SS) jointly modulate ghrelin's action.

History to the discovery of ghrelin.

The most important initial historical time points in the development of the enlarging ghrelin system were 1973, 1976, 1982, 1984, 1990, 1996, 1998, and 1999. At these respective times, the following occurred sequentially: isolation of somatostatin, discovery of unnatural growth-hormone-releasing peptides (GHRPs), isolation of growth-hormone-releasing hormone (GHRH), hypothesis of a new natural GHRP different from GHRH, GHRP+GHRH synergism in humans, discovery of the growth hormone secretagogue GHS/GHRP receptor, cloning of the receptor, and finally, isolation and identification of the new natural endogenous GHRP ghrelin. To understand the pharmacology and probably also the physiological regulation of growth hormone (GH) secretion, an important finding was that GHRP increased pulsatile GH secretion in children as well as normal younger and older men and women.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice.

Objective: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors.

Materials And Methods: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice.

Results: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.

Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation.

Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs.

Gender, sex-steroid, and secretagogue-selective recovery from growth hormone-induced feedback in older women and men.

Context: GH negatively regulates its own secretion. How gender, sex steroids, and secretagogues modulate GH autofeedback is not known.

Hypothesis/objective: Supplementation with sex steroids and/or a peptidyl secretagogue will enhance the escape of GH from autoinhibition, thus framing a mechanism for amplifying pulsatile GH secretion.

Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp.

To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E(2); women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design.

Integrating GHS into the Ghrelin System.

Oligopeptide derivatives of metenkephalin were found to stimulate growth-hormone (GH) release directly by pituitary somatotrope cells in vitro in 1977. Members of this class of peptides and nonpeptidyl mimetics are referred to as GH secretagogues (GHSs). A specific guanosine triphosphatate-binding protein-associated heptahelical transmembrane receptor for GHS was cloned in 1996.

Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion.

Design: While androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, placebo and testosterone, testosterone and dutasteride (to block 5alpha-reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebo-controlled, prospectively randomized design.

Methods: Subjects received i.

Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.

Context: GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion.

Hypothesis: Age, independently of abdominal visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH secretion driven by physiological (rather than pharmacological) amounts of GHRP and GHRH in an experimentally controlled estradiol (E(2)) milieu.

Design And Setting: A prospectively randomized, double-blind parallel-cohort study was conducted at an academic medical center.

Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women.

Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E(2)) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE (n = 20) and POST (n = 22) women underwent a low- vs.

Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism.

Background: Somatostatin (SS), GHRH, GH-releasing peptide (GHRP), and the sex-steroid milieu regulate GH secretion.

Objective: To test whether GHRH and GHRP remain effective secretagogs in the face of short-term hypogonadism.

Design: Prospective, randomized double-blind.

Factors other than sex steroids modulate GHRH and GHRP-2 efficacies in men: evaluation using a GnRH agonist/testosterone clamp.

Background: Sex steroids are prominent regulators of pulsatile GH secretion.

Hypothesis: An experimentally controlled sex-steroid milieu will permit detection of nonsteroidal factors that determine GH secretion.

Subjects: Eleven young (age, 24 +/- 0.

Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp.

Background: Sex steroids influence GH secretion in complex ways.

Hypothesis: Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion.

Context: The study was conducted in a tertiary medical center.

The effect of growth hormone releasing peptide-2 on upper gastrointestinal contractile activity and food intake in conscious dogs.

Background: The aim of this study was to evaluate the effect of growth hormone releasing peptide (GHRP)-2, a synthetic ligand for the growth hormone secretagogue receptor, on upper gastrointestinal motility and food intake.

Methods: Five neurally intact dogs and five dogs with vagotomy and pyloroplasty were equipped with strain gauge force transducers on the stomach, duodenum and jejunum. GHRP-2 (0.

Determinants of GH-releasing hormone and GH-releasing peptide synergy in men.

Age, sex steroids, and abdominal-visceral fat (AVF) jointly affect pulsatile growth hormone (GH) secretion. Pulsatile GH secretion in turn is controlled by GH-releasing hormone (GHRH), GH-releasing peptide (GHRP), and somatostatin. Marked stimulation of pulsatile GH secretion is achieved via GHRH-GHRP synergy.

Aromatase and 5alpha-reductase inhibition during an exogenous testosterone clamp unveils selective sex steroid modulation of somatostatin and growth hormone secretagogue actions in healthy older men.

Background: How endogenous testosterone (Te), 5alpha-dihydrotestosterone (DHT), and estradiol (E(2)) regulate pulsatile GH secretion is not understood.

Hypothesis: Conversion of Te to androgenic (Te-->DHT) or estrogenic (Te-->E(2)) products directs GH secretion. SUBJECTS AND LOCATION: Healthy older men (N = 42, ages 50-79 yr) participated at an academic medical center.

Estrogen elevates the peak overnight production rate of acylated ghrelin.

Context: Acylated ghrelin is the putatively bioactive GH secretagogue.

Hypothesis: Estradiol (E2) stimulates the synthesis rather than inhibits the metabolic clearance of acylated ghrelin.

Setting: The study took place at an academic medical center.