Extrapituitary growth hormone synthesis in humans (original) (raw)
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Extrapituitary growth hormone and growth?
General and Comparative Endocrinology, 2014
While growth hormone (GH) is obligatory for postnatal growth, it is not required for a number of growthwithout-GH syndromes, such as early embryonic or fetal growth. Instead, these syndromes are thought to be dependent upon local growth factors, rather than pituitary GH. The GH gene is, however, also expressed in many extrapituitary tissues, particularly during early development and extrapituitary GH may be one of the local growth factors responsible for embryonic or fetal growth. Moreover, as the expression of the GH receptor (GHR) gene mirrors that of GH in extrapituitary tissues the actions of GH in early development are likely to be mediated by local autocrine or paracrine mechanisms, especially as extrapituitary GH expression occurs prior to the ontogeny of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of GH in embryos has also been shown to be of functional relevance in a number of species, since the immunoneutralization of endogenous GH or the blockade of GH production is accompanied by growth impairment or cellular apoptosis. The extrapituitary expression of the GH gene also persists in some central and peripheral tissues postnatally, which may reflect its continued functional importance and physiological or pathophysiological significance. The expression and functional relevance of extrapituitary GH, particularly during embryonic growth, is the focus of this brief review.
Growth hormone-releasing hormone: Extrapituitary effects in physiology and pathology
Cell Cycle, 2010
The existence of growth hormone-releasing hormone (GHRH) was first suggested in 1961, 1 but the breakthrough for the identification of this hormone was provided by the demonstration of the ectopic production of GHRH by carcinoid and pancreatic tumors. The 44-amino-acid forms of GHRH were then first isolated and characterized from human pancreatic tumors that caused acromegaly 3 and GHRH was only subsequently identified from human and animal hypothalami. GHRH belongs to a family of related peptides that includes vasoactive intestinal peptide (VIP), pituitary adenylate cyclaseactivating peptide (PACAP), secretin, glucagon, glucagon-like peptides-1 and -2, and gastric inhibitory peptide. 3 Peptides in this family act to stimulate the intracellular accumulation of cAMP with the resultant activation of protein kinase A. 5,6 The full intrinsic biological activity of GHRH is retained by the *Correspondence to: Andrew V. Schally;
Factors Regulating Growth Hormone Secretion in Humans
Endocrinology and Metabolism Clinics of North America, 2007
Growth hormone (GH) secretion is pulsatile in nature in all species. The periodic pattern of GH release plays an important role in transmitting the GH message in a tissue-specific manner. For example, only pulsatile GH can normalize muscle and cartilage insulin-like growth factor (IGF)-1 mRNA levels [1] and only the continuous component of GH's secretory profile induces hepatic mRNAs for certain cytochrome P-450 enzymes [2]. The question of what regulates the pulsatile GH secretion pattern is an issue of not only theoretical interest but of considerable practical importance for designing different GH therapies for a variety of human diseases. GH synthesis and secretion are regulated primarily by the hypothalamic neuropeptides growth hormone-releasing hormone (GH-RH) and somatotropin release-inhibiting factor (somatostatin [SRIF]). Similar to other endocrine systems, the end product of GH's action, IGF-1, exerts a negative feedback effect on GH secretion. The amount of GH secreted and the pattern of its release is also subject to the nutritional state and to nutrients themselves and to the prevailing gonadal steroid milieu. Additionally, the recently discovered gastric hormone, ghrelin, may play a role. All these factors interact with each other in a precise and coordinated manner and the interplay between them is necessarily complex. This article provides a brief introductory overview of the different regulators of GH secretion and concentrates primarily on human studies.
The Journal of Clinical Endocrinology & Metabolism, 2001
GH-releasing peptides (GHRPs) are synthetic peptides that bind to specific receptors and thereby stimulate the secretion of pituitary GH. In vivo it is uncertain whether these peptides act directly on somatotroph cells or indirectly via release of GHRH from the hypothalamus. In this study we compared the pituitary hormone response to GHRP-2 in 11 individuals with isolated GH deficiency (GHD) due to a homozygous mutation of the GHRH receptor (GHRH-R) gene and in 8 normal unrelated controls. Basal serum GH levels were lower in the GHD group compared with controls [0.11 Ϯ 0.11 (range, Ͻ0.04 to 0.38) vs. 0.59 Ϯ 0.76 g/L (range, 0.04-2.12 g/L); P ϭ 0.052]. After GHRP-2 administration there was a 4.5-fold increase in serum GH relative to baseline values in the GHD group (0.49 Ϯ 0.41 vs. 0.11 Ϯ 0.11 g/L; P ϭ 0.002), which was significantly less than the 79-fold increase in the control group (46.8 Ϯ 17.6 vs. 0.59 Ϯ 0.76 g/L; P ϭ 0.008). Basal and post-GHRP-2 serum levels of ACTH, cortisol, and PRL were similar in both groups. Basal levels of serum TSH were significantly higher in the GHD group than in the control group (3.23 Ϯ 2.21 vs. 1.37 Ϯ 0.34 IU/mL; P ϭ 0.003). TSH levels in both groups did not change after GHRP-2 administration. These results suggest that an intact GHRH signaling system is not an absolute requirement for GHRP-2 action on GH secretion and that GHRP-2 has a GHRH-independent effect on pituitary somatotroph cells.
The Journal of biological chemistry, 1990
We have recently established that the human growth hormone-variant (hGH-V) gene is functional in vivo by documenting its expression in the placenta. We have subsequently generated transformed murine cell lines stably expressing the genes for normal pituitary growth hormone (hGH-N), hGH-V, and each of two chimeric genes generated by exon 3 exchanges, hGH-NV3 and hGH-VN3. In the present study, we utilize these cell lines as sources of hormone to characterize and compare the receptor binding profiles of hGH-N with hGH-V. hGH-V was found to displace 125I-ovine prolactin bound to rat liver microsomes (lactogen binding) and to displace 125I-hGH bound to rabbit liver microsomes (somatogen binding). Therefore, hGH-V would be predicted to display both somatogenic and lactogenic bioactivity, a dual specificity previously thought to be unique to hGH-N. The concentrations of hormone necessary to displace 50% (IC50) of the 125I-hGH from somatogen receptors and 125I-ovine prolactin from lactogen ...
Bioactive growth hormone in humans: Controversies, complexities and concepts
Growth hormone & IGF research, 2020
To revisit a finding, first described in 1978, which documented existence of a pituitary growth factor that escaped detection by immunoassay, but which was active in the established rat tibia GH bioassay. Methods: We present a narrative review of the evolution of growth hormone complexity, and its bio-detectability, from a historical perspective. Results: In humans under the age of 60, physical training (i.e. aerobic endurance and resistance training) are stressors which preferentially stimulate release of bioactive GH (bGH) into the blood. Neuroanatomical studies indicate a) that nerve fibers directly innervate the human anterior pituitary and b) that hind limb muscle afferents, in both humans and rats, also modulate plasma bGH. In the pituitary gland itself, molecular variants of GH, somatotroph heterogeneity and cell plasticity all appear to play a role in regulation of this growth factor. Conclusion: This review considers more recent findings on this often forgotten/neglected subject. Comparison testing of a) human plasma samples, b) sub-populations of separated rat pituitary somatotrophs or c) purified human pituitary peptides by GH bioassay vs immunoassay consistently yield conflicting results.
Neuroendocrine regulation of growth hormone
European Journal of Endocrinology, 1995
This short review is focused on the neuroendocrine regulation of growth hormone (GH) pulsatile secretory pattern and GH gene expression. The neuronal network involved in the central control of GH includes extrahypothalamic neurons such as the noradrenergic and cholinergic systems, which regulate the two antagonistic neurohormonal systems: somatostatin (SRIH) and GH-releasing hormone (GHRH). Intrahypothalamic Proopiomelanocortin- and Galanin-containing interneurons also participate in the regulation of SRIH and GHRH neuronal activity, which also is dependent on sex steroids and GH and/or insulin-like growth factor I (IGF-I) feedback. cAMP (controlled mainly by GHRH and SRIH), thyroid and glucocorticoid hormones. IGF-I and activin are among the factors that regulate GH gene expression at the transcriptional level and may play a role in somatotroph differentiation and proliferation during ontogeny as well as physiological and pathological states such as acromegaly.