Corticotropin-Releasing Factor and Gonadotropin-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey

Abstract

The effect of corticotropin-releasing factor (CRF) on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, the central neuronal system governing pulsatile pituitary luteinizing hormone (LH) secretion, was studied electrophysiologically in 6 ovariectomized rhesus monkeys bearing bilateral arrays of recording elecrodes implanted in the mediobasal hypothalamus. ‘Volleys’ of increased multiunit activity (MUA) were recorded for 6–10 h in animals placed in primate chairs. The circulating concentrations of LH and cortisol were determined by radioimmunoassay in blood samples taken every 10 min for 3–4 h prior to the administration of CRF (200 µg, i.v.) and for 3–6 h thereafter. CRF resulted in a significant decrease in the frequency of pulse generator activity in 4 of 6 animals, a significant decrease in the duration of MUA volleys and a rise in circulating cortisol levels in all 6 monkeys. Treatment with metyrapone (30 mg/kg, i.m.), an inhibitor of adrenal steroidogenesis that prevented the CRF-induced rise in serum cortisol levels, did not reverse the inhibitory effects of CRF on the frequency or duration of MUA volleys. The opiate antagonist naloxone (0.8 mg/kg, i.v., 10 min prior to CRF followed by 0.8 mg/kg/h infusion) blocked the effects of CRF on MUA volley frequency in 2 of 3 animals, but failed to block the effect of CRF on MUA volley duration, suggesting that endogenous opioids may mediate the action of CRF on pulse generator frequency but not on duration.

Glucocorticoid counteracts the suppressive effect of tumor necrosis factor-alpha on the surge of luteinizing hormone secretion in rats

“…Although CRH has been regarded to be inhibitory towards reproductive function (Rivier & Vale 1984, Rivier et al 1986, Williams et al 1990, we have previously shown that intracerebroventricular injection of -helical CRH enhanced the TNF--induced suppression of the GnRH pulse generator (Yoo et al 1997a). In addition, we have also shown that glucocorticoid maintains pulsatile secretion of LH under infectious stress conditions (Matsuwaki et al 2003).…”

“…There are many reports suggesting that the former is the cause of the latter: for example, both corticotropin-releasing hormone (CRH) (Rivier & Vale 1984, Rivier et al 1986, Williams et al 1990) and glucocorticoid (Baldwin 1979, Briski & Sylvester 1994, McGivern & Redei 1994 have been shown to suppress pulsatile luteinizing hormone (LH) secretion in rats and monkeys. We have previously shown, however, that suppression of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity by tumor necrosis factor-(TNF-), which is one of the major cytokines responsible for the coordination of host defence mechanisms (Michie et al 1988, Sanna et al 1995, Yoo et al 1997b, was enhanced by -helical CRH, a CRH receptor antagonist (Yoo et al 1997a).…”

Single unit components of the hypothalamic multiunit electrical activity associated with the central signal generator that directs the pulsatile secretion of gonadotropic hormones.

“…1) have been recorded from this area in the rhesus monkey (4), rat (5), and goat (6). The unitary association between luteinizing hormone pulses and these electrical signals has been observed in a variety of experimental circumstances (4,(7)(8)(9)(10)(11) as well as during the normal menstrual cycle (12) and has permitted the conclusion that these MUA volleys are the electrophysiological manifestations of GnRH pulse generator activity.…”

Duration of phasic electrical activity of the hypothalamic gonadotropin-releasing hormone pulse generator and dynamics of luteinizing hormone pulses in the rhesus monkey.

“…The onset of each MUA volley is associated with the initiation of a pulse of luteinizing hormone (LH) in the peripheral circulation. In intact animals, the MUA volley is essentially limited to the overshoot and persists for 1-3 min (5). Estradiol given to ovariectomized monkeys reduces the duration of MUA volleys to that characteristic of intact animals (4), as does morphine (3,6) and corticotropin-releasing factor (CRF) (7), while pentobarbital anethesia results in increased MUA volley duration (2).…”