Acute Sex Differences in Serum LH Levels in Gonadectomized Rats: Investigation of Pituitary Response to GnRH Pulse Frequency and Prolactin Secretion as Etiological Agents

Abstract

Gonadectomy results in a striking sex difference in plasma LH levels in adult rats; by 2 days postgonadectomy, serum LH is 5- to 10-fold higher in males than in females. Despite 25 years of work, the site of this sex difference has yet to be determined. Since gonadectomy elevates GnRH pulse frequency, we asked whether a sex difference in pituitary LH secretory response to GnRH pulse frequency underlies the sex difference in serum LH postgonadectomy. Pituitaries from intact and 2-day postgonadectomized male and female rats were perifused for 8 h, receiving either no GnRH (basal) or GnRH pulses (50 ng/ml) at 1 pulse/1.5 h, 1/h or 2/h. Five-minute perifusate fractions were analyzed for LH, FSH, and PRL by RIA. At 1 GnRH pulse/1.5 h, but not other frequencies, pituitaries from gonadectomized males released 1.4-2.8 times more LH per pulse than female pituitaries. Such in vitro sex differences in LH release were not due to higher in vitro prolactin release by female than male pituitaries as suppression of pituitary prolactin secretion by perifusion with the dopamine agonist bromocriptine failed to erase sex differences. Since GnRH pulse frequency in vivo exceeds 1/h following castration, it is unlikely that weak sex differences at frequencies slower than 1/h are relevant to differences in serum LH. In conjunction with prior pituitary studies in this laboratory, these data conclusively demonstrate that the pituitary is not the site of acute sex differences in serum LH levels following gonadectomy. Previous in vitro work indicates that higher GnRH amplitudes elicit higher gonadotropin release, suggesting that differences in the relative amounts of GnRH released by male and female hypothalami may underlie the gender differences observed in serum LH levels immediately postgonadectomy.

Maximal Expression of Foxl2 in Pituitary Gonadotropes Requires Ovarian Hormones

“…Treatment with Antide almost completely blocks the post-OVX increase in Fshb mRNA. This result is consistent with the known increase in GnRH pulse frequency that occurs after OVX that is due to a loss of negative feedback from gonadal steroids [ 54 , 55 ]. Although removal of the ovary also reduces serum inhibin, its loss appears to contribute only marginally to the increase in Fshb mRNA given the almost complete block of the post-OVX rise that occurs after Antide treatment.…”

The 1994 Stevenson Award Lecture. Follicle-stimulating hormone and luteinizing hormone: a tale of two gonadotropins

“…GnRH increases secretion of both LH and FSH in vitro in a dose-dependent manner; both LH and FSH under periffasion conditions (when clearance of both is the same) follow GnRH pulses faithfully (Elshs et al 1995). The maximum secretion rate over basal is greater for LH secretion than for FSH, as is seen in vivo (Suter and Schwartz 1985a, 19858).…”

“…The maximum secretion rate over basal is greater for LH secretion than for FSH, as is seen in vivo (Suter and Schwartz 1985a, 19858). Pituitaries removed at estrus show lower GnRH-stimulated LH release than when removed the day before; however, FSH release is sustained at estrus in vitro (Fallest and Schwartz 1990), reflecting the secondary FSH surge. NBY (neuropeptide Y) given to proestrous pituitaries enhances GnRH response of both LH and FSH, but at metestrus, progesterone and NPY suppress FSH response to GnRH, but not LH response (Knox et al 1995).…”

“…Stimulation of specific areas of the hypothalamus can lead to differential FSHiLH ratios (Chappel 1987), but we do not h o w whether this is due to a specific FSH-RF or to a change in GnRH pulse frequency. Secretion of FSH from isolated pituitaries in the absence of GnRH persists longer than secretion of LH (Sheridan et al 1979;Fallest and Schwartz 1990), probably as a result of local production of activin (Corrigan et al 1991 ;Bilezikjian et al 1993aBilezikjian et al , 1993bDePaolo et d. 1992). Other peptides such as gdanin, substance P, and NPY (Crowley et al 1987) enhance pituitary secretion of LH in response to GnRH in vitro, but FSH secretion also rises (Bauer-Dmtoin et al 1992).…”