Effects of orchidectomy on levels of the mRNAs encoding gonadotropin-releasing hormone and other hypothalamic peptides in the adult male rhesus monkey (Macaca mulatta)

The testicular regulation of luteinizing hormone (LH) secretion in the adult rhesus monkey is mediated by an indirect action of testosterone to decelerate pulsatile gonadotrophin releasing hormone (GnRH) release. Whether this negative feedback action of testosterone involves regulation of GnRH gene expression is unknown, Therefore, the effect of bilateral orchidectomy on hypothalamic levels of the mRNA encoding this hypophysiotropic factor was examined. The feedback action of testosterone is generally considered to be mediated through non-GnRH cells, and the present experiment provided the opportunity to also examine testicular influences on mRNAs encoding putative hypothalamic factors implicated in the testicular regulation of LH secretion. Adult male rhesus monkeys were orchidectomized (n = 5) or sham-orchidectomized (n = 5) and killed 6 weeks later, after a castration-induced hypersecretion of LH was established. Separate preoptic and mediobasal hypothalamus containing areas were collected, and levels of GnRH mRNA, as well as those of mRNAs encoding pro-opiomelanocortin (POMC), the gamma-aminobutyric acid (GABA) synthesizing enzymes (glutamic acid decarboxylase 65 and 67; GAD65 and GAD67, respectively), neuropeptide Y, galanin and transforming growth factor (TGF)alpha, were quantified using RNase protection assay, Values were expressed in terms of optical density relative to that of cyclophilin mRNA levels. Bilateral orchidectomy produced a significant increase in GnRH mRNA levels that was restricted to the mediobasal hypothalamus and that was associated with a significant decrease in POMC, GAD65 and GAD67 mRNA levels in this region of the hypothalamus. In contrast, neuropeptide Y, galanin and TGF alpha mRNA levels were not affected by castration. These results indicate that, in the monkey, the deceleration of pulsatile GnRH release that is imposed by the testis, and presumably mediated by testosterone, is associated with a concomitant down regulation of GnRH gene expression in the mediobasal hypothalamus, They also support the notion that this hypothalamic feedback action may be mediated by POMC-and GABA-producing neurones in the mediobasal hypothalamus.