Pulsatile follicle-stimulating hormone secretion is independent of luteinizing hormone-releasing hormone (LHRH): pulsatile replacement of LHRH bioactivity in LHRH-immunoneutralized rats

Abstract

We recently reported that passive immunoneutralization of endogenous LHRH in castrate male rats completely abolishes pulsatile LH secretion and, within 1 h, lowers mean plasma LH by 86%. While pulsatile FSH secretion, in terms of pulse amplitude and frequency, is not affected, mean plasma FSH is gradually lowered but only by 49% after 24 h. In the present study, we have examined the effect of replacing pulsatile LHRH biological activity on LH and FSH secretion in 4-week castrate male rats in which endogenous LHRH has been immunoneutralized by ovine anti-LHRH serum 772 (LHRH-AS) for 24 h. The LHRH-AS requires the 3-10 amino acid sequence of LHRH including the amidated C terminus for complete recognition. In order to circumvent the antiserum blockade, we utilized the LHRH agonist [Des Gly10]-LHRH ethyl amide (DG-LHRH) which is minimally recognized by the LHRH-AS but which possesses 2.6-fold the LH-releasing activity of LHRH. Twenty-four hours after injecting 500 microliter LHRH-AS into cannulated, castrate rats, sequential blood samples were taken every 10 min for 4 h. Bolus 3-ng injections of either DG-LHRH or saline were given iv either every 30 min during the 4-h collection period or every 30 or 60 min for 10 h before the initiation of and continuing through the 4-h collection period. Each DG-LHRH injection stimulated the release of a single pulse of LH, while pulsatile FSH secretion was unaffected. No synchrony was observed between the DG-LHRH pulses and the endogenous FSH pulses. Short term DG-LHRH treatment partially restored, and long term DG-LHRH treatment every 60 min completely restored, mean plasma FSH to the level observed in nonantiserum-treated castrate control rats. Long term DG-LHRH treatment every 30 min caused a rise in mean plasma FSH which exceeded the plasma FSH level of the nonantiserum-treated controls. The mean plasma level of LH was entirely dependent on the frequency of the DG-LHRH injection. The results of this study clearly demonstrate that pulsatile FSH secretion is independent of LHRH but that LHRH is required to elevate and/or maintain high mean plasma FSH levels. Trough levels of LH, however, are dependent on the frequency of LHRH-induced pulsatile LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)