Mice Are Insensitive to the Antitesticular Effects of Luteinizing Hormone-Releasing Hormone Agonists*

Abstract

Treatment of male rats with [(imBzl)-D-His6, Pro9-NEt]LHRH or [D-Trp6,Pro9-NEt]LHRH, potent agonists of LHRH, led to a marked decrease in serum testosterone levels and a reduction in testicular LH receptor concentration. Similar treatment of mice showed that they were resistant to the antitesticular effects of the LHRH agonists. To further explore the differences between rats and mice, the direct antitesticular effects of these peptides were investigated in hypophysectomized animals. Hypophysectomized rats and mice were given ovine FSH (50 micrograms), with or without a LHRH agonist (10 micrograms), daily for 5 days. On day 6, the testicular steroidogenic response to hCG was studied. In these studies the in vivo as well as the in vitro steroidogenic response of rat testes to hCG were inhibited by the LHRH analogs. In contrast, pretreatment of mice with the LHRH analogs did not affect their testicular steroidogenic response. Binding studies with the [125I]LHRH analog demonstrated receptors for this peptide on Leydig cells from adult rats. Receptors for LHRH were not, however, detectable on murine Leydig cells. These results suggest that one of the reasons for the lack of an antitesticular effect of LHRH agonists in mice may be due to the inability of these peptides to have a direct effect on testes and may relate to a lack of LHRH receptors.

Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice

“…Contrasting with the Gnrhr gene in the rat testis and with the rat promoter ALPP fusion transgene in the mouse testis, the endogenous mouse Gnrhr is expressed at very low levels in the gonads. These data are consistent with previous works illustrating the lack of detection of GnRH-binding sites in the foetal (Pointis & Latreille 1986) as well as adult (Wang et al 1983) mouse testis, the absence of functional consequences after Gnrhr disruption (Wu et al 2010) and the low activity of the 1.9 kb mouse Gnrhr promoter in the testis of transgenic mice. Indeed, the latter was estimated to be about 1:100 Rat Gnrhr promoter 3.85× 3.68× 3.54×…”

Absence of direct effects of GnRH on testicular steroid secretion in the ram

“…For rams in the non-breeding season, arterial blood supply averages 8-8 ± 0-9 ml/min per testis (Noordhuizen-Stassen, 1984) which for both testes approximates 0-4-0-5% of the heart minute volume. (Hsueh & Erickson, 1979;Clayton et al, 1980;Sharpe, 1982Sharpe, , 1984, but is in accordance with reports on other species (Wang et al, 1983;Schaison et al, 1984 (Clayton & Huhtaniemi, 1982), primate, cow, sheep and pig (Brown & Reeves, 1983) (Lincoln, 1978;Wu et al, 1987), 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. Assuming uniform mixing of the GnRH and no immediate metabolism, the concentration in the general circulation after injection of 25 ng will approximate 6-25 pg/ml in a 50-kg ram with an estimated blood volume of 4000 ml (8% of body weight).…”

Fetal expression of GnRH and GnRH receptor genes in rat testis and ovary

“…In the fetal testis, the onset of the main steroidogenic enzyme genes expression, and particularly of 17 -hydroxylase, occurs around 15·5 dpc (Majdic et al 1996), and thus early steroidogenesis, as GnRH and GnRH-R genes expression, is independent of gonadotropins (ElGehani et al 1998). We also point out that in the mouse, a species that lacks the gonadal GnRH-R (Wang et al 1983), there is no decline in testosterone production in late fetal life (O'Shaughnessy et al 1998).…”