Relative Effect of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Gonadotropin Release

Abstract

Two forms of GnRH (GnRH-I and GnRH-II) are expressed in the hypothalamus of humans and rhesus monkeys, but their relative abilities to stimulate LH and FSH release are unknown. Therefore, young (8 -12 yr) and old (21-23 yr) female rhesus monkeys were treated iv with bolus injections of either GnRH-I or GnRH-II (dose range, 0.01-10 g/kg body weight); serial blood samples were remotely collected through a vascular catheter for up to 2 h after injection. Overall, plasma LH concentrations were similarly elevated after treatment with GnRH-I and GnRH-II, and the responses were slightly greater in the younger animals. Although plasma FSH concentrations were unaffected by a single exposure to GnRH-I or GnRH-II, they showed a similar significant increase after repeated exposures (every 2 h for 24 h). In a subsequent experiment, antide, a GnRH-I receptor antagonist, was administered (100 g/kg body weight) together with a single injection of GnRH-I or GnRH-II (1 g/kg body weight). As expected, GnRH-Iinduced LH release was significantly attenuated by this combined treatment; moreover, GnRH-II-induced LH release was completely blocked. Taken together, these data show that GnRH-II can potently stimulate gonadotropin release in vivo and that this action is likely mediated through the GnRH-I receptor. (J Clin Endocrinol Metab 88: 2126 -2134, 2003)

Retention and Silencing of Prepro-GnRH-II and Type II GnRH Receptor Genes in Mammals

“…Perhaps the GnRH-II–type I GnRH receptor interaction may be important in vivo. Partial support for this possibility is the demonstration that intravenous administration of GnRH-II can induce release of LH via activation of the type I GnRH receptor [58]. However, for this ligand-receptor interaction to be physiologically relevant, the GnRH-II neurons must reach the vicinity of the hypothalamic median eminence.…”

Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans

“…A number of amino acid residues of critical importance for receptor function have been identified in the human GnRH receptor. For instance, Ala (261) in the third intracellular loop is crucial for G protein coupling and receptor internalization (82), whereas Asp (98), Trp (101), Asn (102), Lys (121), Asn (212), and Asp (302) are important for ligand binding (83-87). In addition, the extra species-specific Lys (191) residue has been shown to be a significant determinant of the expression and internalization of the human GnRH receptor (88).…”

“…Recently, GnRH-II has also been shown to be capable of stimulating LH and FSH release both in vivo (261) and in cultured pituitary cells (262). This stimulation is mediated via activation of the type I GnRH receptor because the effects can be blocked by antide (261,262).…”

Contribution of Chicken GnRH-II and Lamprey GnRH-III on Gonadotropin Secretion

“…However, the in vitro effect of cGnRH-II on gonadotropin secretion was less potent than that of mGnRH (Okada et al, 2003). In contrast, in vivo exogenous doses of mGnRH and cGnRH-II in female rhesus monkeys were equally potent at stimulating LH release with little effect on FSH secretion (Densmore and Urbanski, 2003). In males and females rhesus monkeys, cGnRH-II mRNA expression in the mediobasal hypothalamus (MBH) significantly increased in adult animals compared with prepubertal macaques (Latimer et al, 2001).…”

“…In fact, when COS-1 or COS-7 cells were transfected with the type II GnRHR, the potency was high for cGnRH-II and low for mGnRH. Nonetheless, in vivo and in vitro work in rhesus monkey (Densmore and Urbanski, 2003;Okada et al, 2003) and pigs , using specific type I GnRHR antagonists (Antide and Cetrorelix) suggest that cGnRH-II can also stimulate gonadotropin secretion via the type I GnRHR (Neill et al, 2004). Figure 1.…”