Thorner et al. (1982) found a patient presented with classic acromegaly and an enlarged pituitary fossa, but the pituitary was hyperplastic, not adenomatous, suggesting stimulation from another source. It was discovered, that the patient had a pancreatic tumor that was stimulating the pituitary. The pancreatic tumor was removed, its GH releasing activity was purified and sequenced, and its cDNA and gene were subsequently cloned (Gubler et al., 1983). NCBI Summary:
The protein encoded by this gene belongs to the glucagon family and is a preproprotein that is produced in the hypothalamus. The preproprotein is cleaved to form a 44 aa factor, also called somatocrinin, that acts to stimulate growth hormone release from the pituitary. Variant receptors for somatocrinin have been found in several types of tumors, and antagonists of these receptors can inhibit the growth of the tumors. Defects in this gene are a cause of dwarfism, while hypersecretion of the encoded protein is a cause of gigantism.
General function
Ligand, Hormone
Comment
Cellular localization
Secreted
Comment
Ovarian function
Ovulation, Steroid metabolism, Oogenesis
Comment
Moretti et a. (1990) demonstrate that GHRH is a potent cAMP-mediated agonist in the rat ovary and acts on a common VIP/GRF receptor in maturing granulosa cells. They suggested that that the potentiating effect of administered GRF on gonadotropin-stimulated follicular development in vivo is in part mediated by direct actions of the peptide on the VIP/GRF receptor. Also, since GRF is present in the gonads, it is possible that the locally-produced peptide promotes follicular maturation by paracrine modulation of the stimulatory action of FSH on granulosa cell function. In follicle-enclosed, cumulus-enclosed and denuded oocytes obtained from immature pregnant mare's serum gonadotropin-treated rats, Apa et al. (1995) demonstrated that the addition of GRF to the cultures significantly accelerated maturation in follicle- and cumulus-enclosed oocytes while no effect was seen on denuded oocytes. The GRF action was probably not mediated by the vasoactive intestinal peptide (VIP) receptors since the two hormones had different effects on oocyte maturation and on cAMP production by granulosa cells. In addition, the disappearance of the GRF effect observed in the presence of antibodies anti-GH suggested that GRF required the intermediacy of GH to accomplish its effect on oocyte maturation. Li et al. (1993) demonstrated that androgen treatment augments growth hormone-releasing hormone-stimulated progestin production by rat granulosa cells.
In contrast, Hugues et al. (1996) showed that co-treatment with GHRH and FSH in vivo induced significant increases in plasma IGF-I concentrations and steroid production by cultured granulosa cells. The addition of GHRH to culture medium did not significantly alter steroid production by either non-differentiated (no FSH in vivo) or differentiated (FSH in vivo) granulosa cells. In contrast, treatment in vitro with IGF-I significantly increased steroidogenesis in both cases. The authors suggest that any physiologically significant effect of GHRH on ovarian function is probably to be exerted via activation of the somatotrophic axis and the subsequent amplification of ovarian FSH responsiveness by IGF-I.Karakji et al. (1995) demonstrated that GHRH treatment stimulates rat granulosa cell plasminogen activator activity in vitro.
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
A GHRH-like peptide has been detected by immunocytochemistry in the human ovary and by
RIA in follicular fluid, suggesting local synthesis of the peptide. Cultured rat granulosa cells released immunoreactive GHRH into the incubation medium (Bagnato et al., 1992). The GHRH immunoreactivity detected in ovarian extracts coeluted on gel filtration chromatography with authentic GHRH (5.2 kilodaltons).