Appraisal of growth hormone (GH) secretion: evaluation of a composite pharmacokinetic model that discriminates multiple components of GH input.

Criteria for a diagnosis of GH deficiency include inadequate GH secretion as assessed by provocative testing. The changes in serum GH concentration in such tests, however, do not uniformly predict treatment responses. We questioned whether the changes in serum GH have a uniform dependence among subjects on the mass of secreted GH.

Effects of gender on exercise-induced growth hormone release.

We examined gender differences in growth hormone (GH) secretion during rest and exercise. Eighteen subjects (9 women and 9 men) were tested on two occasions each [resting condition (R) and exercise condition (Ex)]. Blood was sampled at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence.

Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis.

Objective: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency.

Design: We used a randomized, double-blind, placebo-controlled design.

Methods: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.

LH and FSH secretory responses to GnRH in normal individuals: a non-parametric deconvolution approach.

Objective: To reconstruct the instantaneous secretion rate (ISR) of LH and FSH after GnRH administration in normal volunteers using non-parametric deconvolution, and to derive a direct integration formula to evaluate the amount of LH and FSH secreted during the first 60 min after the stimulus.

Design And Methods: First, the deconvolution method was validated in vivo by reconstructing doses ranging from 7.5 IU to 75 IU injected in three healthy adult volunteers whose endogenous LH had previously been downregulated by pretreating them, 3-4 weeks earlier, with 3.

Impact of acute exercise intensity on pulsatile growth hormone release in men.

To investigate the effects of exercise intensity on growth hormone (GH) release, 10 male subjects were tested on 6 randomly ordered occasions [1 control condition (C), 5 exercise conditions (Ex)]. Serum GH concentrations were measured in samples obtained at 10-min intervals between 0700 and 0900 (baseline) and 0900 and 1300 (exercise+ recovery). Integrated GH concentrations (IGHC) were calculated by trapezoidal reconstruction.

Low-dose T(3) improves the bed rest model of simulated weightlessness in men and women.

This study tested the hypothesis that low-dose 3,5, 3'-triiodothyronine (T(3)) administration during prolonged bed rest improves the ground-based model of spaceflight. Nine men (36.4 +/- 1.

Time mode of growth hormone (GH) entry into the bloodstream and steady-state plasma GH concentrations, rather than sex, estradiol, or menstrual cycle stage, primarily determine the GH elimination rate in healthy young women and men.

We have investigated whether a reduced MCR of GH in women will account for their higher serum GH concentrations premenopausally compared with those in men. To this end, we directly compared the half-life (t 1/2) of GH and its volume of distribution (Vo) in 13 young men and 6 comparably aged women, each evaluated at three stages of the normal menstrual cycle (viz. the early follicular, late follicular, and midluteal phases).

Tripartite neuroendocrine activation of the human growth hormone (GH) axis in women by continuous 24-hour GH-releasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms.

Despite the discovery of potent GH-releasing peptides (GHRPs) more than 15 yr ago and the recent cloning of human, rat, and pig GHRP receptors in the hypothalamus and pituitary gland, the neuroregulatory mechanisms of action of GHRP agonists on the human hypothalamo-somatotroph unit are not well delineated. To gain such clinical insights, we evaluated the ultradian (pulsatile), entropic (pattern orderliness), and nyctohemeral GH secretory responses during continuous 24-h i.v.

Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis.

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern.

Disruption of the pulsatile and entropic modes of insulin release during an unvarying glucose stimulus in elderly individuals.

Insulin is secreted in a pulsatile fashion with measurable orderliness (low entropy). Aging is characterized by alterations in pulsatile insulin release in the fasting state. We undertook the current studies to determine whether disruptions in pulsatile insulin release in response to sustained glucose infusion also accompany the age-related changes in carbohydrate metabolism.

Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion.

The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen's specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers (n = 9) received randomly ordered placebo versus estradiol-17beta (1 mg micronized steroid twice daily orally) treatment for 7-10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay.

Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat.

Design: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.

Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas.

To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis.

Reactivation of pituitary hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness.

Protracted critical illness is marked by protein wasting resistant to feeding, by accumulation of fat stores, and by suppressed pulsatile release of GH and TSH. We previously showed that the latter can be reactivated by brief infusion of GH-releasing peptide (GHRP-2) and TRH. Here, we studied combined GHRP-2 and TRH infusion for 5 days, which allowed a limited evaluation of the metabolic effectiveness of this novel trophic endocrine strategy.

Mechanisms subserving the physiological nocturnal relative hypoprolactinemia of healthy older men: dual decline in prolactin secretory burst mass and basal release with preservation of pulse duration, frequency, and interpulse interval--a General Clinical Research Center study.

Increasing age is accompanied by decrements in randomly obtained, fasting, or frequently sampled serum PRL concentrations. The precise neuroendocrine mechanisms underlying such relative hypoprolactinemia in aging are incompletely understood. In the present study, we sampled blood at 2.

Short-term fasting suppresses leptin and (conversely) activates disorderly growth hormone secretion in midluteal phase women--a clinical research center study.

Short term fasting activates the corticotropic and somatotropic, and suppresses the reproductive, axis in men. Analogous neuroendocrine responses are less well characterized in women. Recently, we identified a negative association between the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH secretion in older fed women.

Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness.

Objective: During prolonged critical illness, nocturnal pulsatile secretion of GH, TSH and prolactin (PRL) is uniformly reduced but remains responsive to the continuous infusion of GH secretagogues and TRH. Whether such (pertinent) secretagogues would synchronize pituitary secretion of GH, TSH and/or PRL is not known.

Design And Methods: We explored temporal coupling among GH, TSH and PRL release by calculating cross-correlation among GH, TSH and PRL serum concentration profiles in 86 time series obtained from prolonged critically ill patients by nocturnal blood sampling every 20 min for 9 h during 21-h infusions of either placebo (n=22), GHRH (1 microg/kg/h; n=10), GH-releasing peptide-2 (GHRP-2; 1 microg/kg/h; n=28), TRH (1 microg/kg/h; n=8) or combinations of these agonists (n=8).

Synchronous fluctuations of blood insulin and lactate concentrations in humans.

Oscillatory organization is a universal mode of signal transduction in living organisms. In vitro studies suggest spontaneous pulsatile fluctuations of intracellular energy metabolism. It is possible that, in vivo, some of these processes are synchronized by the pulsatile release of insulin.

Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome.

The aim of this study was to quantify pulsatile LH secretion, burst frequency and mass, LH half-life, and the approximate entropy (ApEn) or (dis-) orderliness of LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high-precision immunofluorimetric LH assay with deconvolution techniques. We sampled LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean +/- S.E.

Evaluation of LH secretory dynamics during the rat proestrous LH surge.

The preovulatory luteinizing hormone (LH) surge results from the integration of complex interactions among gonadal steroids and hypothalamic and pituitary hormones. To evaluate changes in LH secretory dynamics that occur during the rat LH surge, we have 1) obtained frequently sampled serum LH concentration time series, 2) used both waveform-dependent and waveform-independent convolution analyses, and 3) independently assessed proestrous LH half-life and basal non-gonadotropin-releasing hormone (GnRH)-dependent LH secretion during the LH surge. Waveform-independent pulse analysis revealed a 24-fold increase in the maximal pulsatile LH secretory rate attained during late proestrus compared with early proestrus.

Concerted regulation of low density lipoprotein receptor gene expression by follicle-stimulating hormone and insulin-like growth factor I in porcine granulosa cells: promoter activation, messenger ribonucleic acid stability, and sterol feedback.

Insulin-like growth factor I (IGF-I) and the gonadotropin, FSH, can synergize to stimulate progesterone production in primary cultures of maturing granulosa cells. These trophic hormones increase low density lipoprotein (LDL) receptor binding and internalization, and the utilization of LDL-borne cholesterol by granulosa cells. To determine whether and how IGF-I and FSH control the genomic expression of the LDL receptor, we evaluated their individual and concerted effects on LDL receptor messenger RNA (mRNA) accumulation, stability, and gene promoter activity in first passage monolayer (serum-free) cultures of porcine granulosa cells.

Mechanisms of insulin-like growth factor I augmentation of follicle-stimulating hormone-induced porcine steroidogenic acute regulatory protein gene promoter activity in granulosa cells.

Insulin-like growth factor I (IGF-I) and the gonadotropin, FSH, can synergize to stimulate progesterone production in primary cultures of maturing human, rat, and pig granulosa cells. These trophic hormones act by increasing the activity and production of proteins and their gene transcripts essential to sterol uptake, delivery, and utilization in steroidogenesis. We previously observed that FSH and IGF-I interact synergistically to promote the accumulation of steroidogenic acute regulatory protein (StAR) messenger RNA and protein in granulosa cells.

Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human.

During the last decade, the GH axis has become the compelling focus of remarkably active and broad-ranging basic and clinical research. Molecular and genetic models, the discovery of human GHRH and its receptor, the cloning of the GHRP receptor, and the clinical availability of recombinant GH and IGF-I have allowed surprisingly rapid advances in our knowledge of the neuroregulation of the GH-IGF-I axis in many pathophysiological contexts. The complexity of the GHRH/somatostatin-GH-IGF-I axis thus commends itself to more formalized modeling (154, 155), since the multivalent feedback-control activities are difficult to assimilate fully on an intuitive scale.

Antenatal glucocorticoids modulate the amplitude of pulsatile cortisol secretion in premature neonates.

We hypothesized that antenatal exposure to glucocorticoids influences subsequent pulsatile cortisol (F) secretion in premature neonates. To test this hypothesis, blood was sampled for plasma F determination via indwelling arterial lines at 15-min intervals for 6 h in 26 clinically stable neonates whose gestational ages were 25-33 wk. Deconvolution analysis was used to characterize F secretion and elimination.