The involvement of ovarian factors in maintaining the pituitary glands of female rats in a state of low LH responsiveness to LHRH

Abstract

The effects of discontinuation and restoration of ovarian influences on the pituitary LH response to LHRH in vitro were investigated. When female rat pituitary glands taken on day 2 of dioestrus were incubated with LHRH the release of LH was low during the first hour (lag phase response) and afterwards a progressive, protein synthesis-dependent increase took place (second phase response), this being the self-priming action of LHRH. Short-term discontinuation (less than 1 day) of ovarian influences on the rat pituitary gland in vivo (ovariectomy) or in vitro (incubation in medium only) resulted in an increased LHRH-induced LH response during the lag phase. The biphasic LH response or the self-priming action of LHRH disappeared completely after long-term discontinuation of ovarian influences on the pituitary gland, LH release being at its maximum from the start of the incubation. The biphasic response was reinstated when ovaries were implanted under the kidney capsules of ovariectomized rats. Auto-implantation of an ovary into the spleen immediately after bilateral ovariectomy did not, however, prevent the disappearance of the LHRH self-priming action. Ovarian activity responsible for the presence of the low LH response during the lag phase was thus effectively removed by the liver, but inhibin-like activity suppressing serum FSH levels remained present. Silicone elastomer implants (s.c.) containing oestradiol-17 beta, implanted for 4 weeks, did not reverse the loss of the biphasic LH response to LHRH. It is concluded that liver-labile factors released by the ovaries keep the pituitary gland in a state of low responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

The ovary-mediated FSH attenuation of the LH surge in the rat involves a decreased gonadotroph progesterone receptor (PR) action but not PR expression

“…The present results first show that ovarian stimulation with hFSH during the dioestrous phase in the cyclic rat decreased serum LH concentration in pro-oestrous afternoon, a basic finding wholly in agreement with previously reported data (Geiger et al 1980, de Koning et al 1987, Culler 1992, Schuiling et al 1999; secondly, that hFSH stimulated the production of some ovarian factor(s) other than E 2 that reduced the preovulatory LH surge, but not basal LH secretion; and thirdly, that the ovary-mediated hFSH inhibition of LH surge was exerted on gonadotroph PR action.…”

“…Although the FSH-dependent ovarian hormones inhibin (Culler 1992, Byrne et al 1995 and follistatin (Wang et al 1990) have been postulated to have GnSI/A bioactivity, the majority of evidence support the view that the inhibitory effect of exogenous FSH on the LH surge is mainly due to the activity of the putative GnSI/AF (de Koning et al 1987, Balen & Jacobs 1991, Balen 1996, Byrne et al 1996, de Koning et al 2001, Fowler et al 2003. GnSI/AF is a nonsteroidal, non-inhibin ovarian hormone of w60-70 kDa (Fowler et al 2003) secreted by granulosa cells in response to FSH with the specific bioactivity of inhibiting LHRH selfpriming (Balen 1996, Fowler et al 2003.…”

Non-steroidal factors in bovine follicular fluid inhibit or facilitate the action of pulsatile administration of GnRH on LH release in the female rat

“…However, distinct pharmacological differences between GnSIF/AF and inhibin bioactivity were observed. First, opposed to inhibin, the liver degrades GnSIF/AF bioactivity (first pass-effect (Uilenbroek et al 1978, de Koning et al 1987). The present results support this finding by showing the importance of the route of administration of bFF to express the GnSIF/AF bioactivity (Fig.…”

“…The LH assay was carried out according to de Koning et al (1987). The sensitivity of the LH assay, defined as the amount of standard required to suppress binding of iodinated LH to 90% of that occurring without unlabelled LH, was estimated as 72 2 (..)…”

“…The antagonistic interaction between GnRH and the ovarian protein, gonadotrophin surge-inhibiting factor or attenuating factor (GnSIF/AF), may be responsible for this tightly controlled LH release (de Koning et al 1979, 1987, 1989, Busbridge et al 1990, Knight et al 1990, Koppenaal et al 1993, Fowler et al 1994, de Koning 1995, van Dieten & de Koning 1995. It was postulated that after each pulse of GnRH, GnSIF/AF neutralizes the potential self-priming action of GnRH before it can become effective, thereby maintaining a state of low LH responsiveness of the gonadotrophs to the action of the next GnRH pulse (de Koning 1995, van Dieten & de Koning 1995.…”