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An Overview of the Biological Actions and Neuroendocrine Regulation of Growth Hormone
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Growth hormone secretory dynamics result from an intricate interchange between somatostatin and growth hormone-releasing hormone (GHRH) secretion from the hypothalamus. GHRH increases growth hormone release,115,116 and somatostatin inhibits its release.117 The results of several studies suggest that both hormones are secreted in a phasic manner, with GHRH contributing to high-amplitude growth hormone pulses and somatostatin being secreted during trough periods.118 The dynamic interrelationship between these hypothalamic hormones is responsible for pulsatile growth hormone secretion. Although somatostatin and GHRH have a critical role in the regulation of growth hormone, other factors contribute to growth hormone release by acting directly on the pituitary gland, by regulating hypothalamic GHRH or somatostatin secretion, or by influencing neurotransmitters that regulate somatostatin and GHRH release.
Drugs of Abuse and Addiction
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Aarushi Singh
Addictive drugs such as cocaine, AMPH (class III drugs) hinder the monoamine transporters of the neurons mainly which are present in the ventral tegmental area (VTA) and blocks the dopamine uptake by them leading to extracellular accumulation of dopamine as illustrated in Figure 20.1. These elevated dopamine concentrations may lead to anterior pituitary hypoplasia, inability to lactate owing to the reduced hypothalamic content of growth hormone-releasing hormone (Amara and Sonders, 1998).
Endocrinology of aging
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
Prasanth N. Surampudi, Christina Wang, Yanhe Lue, Ronald Swerdloff
GH is secreted by pituitary somatotrophs in a pulsatile manner. Growth hormone–releasing hormone (GHRH) stimulates the transcription of GH. Some of the other stimulatory factors on GH release include ghrelin, amino acids, hypoglycemia, slow waves during sleep, malnutrition, and stress. The maximal secretion of GH occurs during the night during slow-wave sleep, particularly when somatostatin release is diminished. GH acts both by direct action and indirectly through IGF-I. IGF-I is synthesized in both in the liver and in the periphery, and it circulates bound to several binding proteins, including insulin-like growth factor–binding protein (IGFBP)-3. The levels of IGF-I influence GH release by directly having inhibitory effects on the pituitary and hypothalamus. It also works indirectly by stimulating somatostatin, which has an inhibitory effect on GH release. The reduction of ghrelin (e.g., during digestion) and increase in circulating nonesterified free fatty acids also have inhibitory effects on GH secretion.
Transient Permeation Enhancer® (TPE®) technology for oral delivery of octreotide: a technological evaluation
Published in Expert Opinion on Drug Delivery, 2021
Tuvia et al. [62] carried out a dose escalation of oral octreotide acetate of 3, 10, and 20 mg versus s.c. administration of an immediate-release octreotide formulation (0.1 mg) in 75 healthy subjects. PK and plasma changes in GH were examined. Dose-related effects on PK were seen with the oral capsule and plasma octreotide was detected within 60 min of dosing in the fasted subjects, similar to the pattern of the rat perfusion studies. The PK profile from the 20 mg capsule was similar to s.c. and a relative oral bioavailability of ~0.7% could be calculated (Figure 4), a lower value than that detected in large animal studies. Plasma half-life (t½) was 2.5 h by both administration routes and the plasma level of octreotide remained within the therapeutic range for 5 h. The capsule was well tolerated, with mild adverse events occurring in 35% of subjects after a single oral dose. Of these, the most noticeable event was abdominal pain in 15% of subjects. The key pharmacodynamic data were that a single dose of the 20 mg octreotide capsule reduced basal GH levels by 49% and suppressed GH levels stimulated by GH Release Hormone (GHRH) by 80%. This study established 20 mg as an initial baseline dose level for reducing plasma GH and it guided the dose level to 40 mg per day in the subsequent patient trials.
The association between insulin-like growth factor 1 levels within reference range and early postoperative remission rate in patients with Cushing’s disease
Published in Endocrine Research, 2021
Emre Gezer, Berrin Çetinarslan, Alev Selek, Zeynep Cantürk, Mehmet Sözen, Özlem Elen, Canan Baydemir, Burak Çabuk, Savaş Ceylan
Both long-term endogenous and exogenous hypercortisolism have been shown to have a suppressive effect on circulating GH.3,5,17,22,29–31 Similarly, the median (25th-75th) concentration of GH was 0.30 (0.12–0.83) ng/mL in our study. Furthermore, there was a significant difference in GH concentrations between the tertiles of IGF-1, with the lowest concentrations in T1 and the highest in T3 (p < .001). Potential mechanisms for this effect have been suggested to be desensitization of pituitary growth hormone releasing hormone (GHRH) receptors or the deterioration of hypothalamic GHRH secretion.5 Nevertheless, the pathophysiological mechanisms elevating IGF-1 in patients with CD, are still unclear. Hyperinsulinism induced by hypercortisolism is one possible mechanism, but Bang et al.19 found increased levels of IGF binding proteins (IGFBPs) in CD and two other studies reported the same outcome. It was hypothesized that increased IGFBPs caused a reduction IGF-1 bioactivity with subsequent enhanced sensitivity of tissue GH receptors leading to increased IGF-1.3,10 Considering all these as a seesaw-like mechanism, our results may indicate that in the majority of CD patients, there has been a positive elevation trend in IGF-1 concentration, possibly due to the increase in IGFBP and a decrease in IGF-1 bioactivity. On the other hand, the increased inhibition of GH due to severe hypercortisolism might dominate the other possible mechanisms, resulting in a final decrease in IGF-1 concentration.
Safety of current recombinant human growth hormone treatments for adults with growth hormone deficiency and unmet needs
Published in Expert Opinion on Drug Safety, 2020
Charlotte Höybye, Paolo Beck-Peccoz, Suat Simsek, Markus Zabransky, Hichem Zouater, Günter Stalla, Robert D Murray
To understand the potential effects, adverse effects, and risks of GH replacement some knowledge of physiology is useful. Serum GH is heterogeneous, consisting of two major forms, the predominant isomer being a 22-KDa peptide consisting of 191 amino acids and four α-helices, and a 20-KDa spliced variant lacking an internal sequence of 15 amino acids, which accounts for around 10% of total GH secretion [4]. It is synthesized and released from the anterior pituitary gland. GH secretion is induced by ghrelin and hypothalamic GHRH (Growth Hormone Releasing Hormone) and inhibited by somatostatin in addition to negative feedback by insulin-like growth factor I (IGF-I) [5]. GH has a half-life of 10–20 minutes and is secreted in pulses throughout the day, with an increased number of pulses during sleep. The release of GH is affected by many different factors, among them age, gender, nutrition, and illness [5]. The largest GH bursts are seen in puberty and the bursts are higher in women than in men. GH increases the production of IGF-I.