Regulation of hypothalamic gonadotropin-releasing hormone secretion in experimental uremia: in vitro studies.
Defective regulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion is the primary defect leading to the inhibition of pituitary gonadotropin secretion and its consequences such as androgen deficiency and infertility in experimental uremia. Previous studies using indirect methods to study presumptive GnRH release and the function of GnRH-secreting neurons have suggested functional disturbances of GnRH neurosecretion; however, the precise biochemical mechanisms involved were not defined. Therefore, in order to clarify the mechanisms of aberrant regulation of hypothalamic GnRH secretion in experimental uremia, we examined basal secretion of GnRH from mediobasal hypothalamus (MBH) in vitro and the GnRH-secretory responses to naloxone, an opiate receptor antagonist in experimental uremia. Using a static incubation system, adult male rats, either intact or castrate, with subtotal nephrectomy demonstrated a significant reduction of GnRH secretion by 25% in intact and by 40% in castrate uremic male rats compared with their nonuremic controls. In contrast, hypothalamic GnRH content of uremic animals was increased significantly (6% in intact and 14% in castrate uremic rats). Despite the fall in basal GnRH release from MBH, the MBH GnRH release response to in vitro stimulation by an opioid blocker (naloxone) and a membrane-depolarizing agent (veratrine) were not diminished in uremic male rats. These findings suggest that the inhibition of pituitary gonadotropin secretion in experimental uremia is likely to be due to a functional defect in suprahypothalamic regulation of GnRH secretion rather than an intrinsic defect in the GnRH-secreting neurons. Further studies are required to clarify the nature of the neuromodulator interactions involved.
Wibullaksanakul
S
S
Department of Obstetrics and Gynecology, University of Sydney, Australia.
Handelsman
D J
DJ
D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013737:Testis / Q000502:physiology; D014511:Uremia / Q000503:physiopathology*; D014702:Veratrine / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D014702:Veratrine