The roles of inhibin and gonadotrophin-releasing hormone in the control of gonadotrophin secretion in the ewe
Authors: Martin G. B. , Wallace J. M. , Taylor P. L. , Fraser H. M. , Tsonis C. G. , McNeilly A. S. 
Published: December 2008

The respective roles and relative importance of ovarian inhibition and hypothalamic stimulation in the differential control of the secretion of FSH and LH were studied in the ewe. In the first experiment two groups of ten intact ewes were injected i.v. twice daily with 9 ml charcoal-extracted bovine follicular fluid (bFF), a preparation rich in inhibin (3·65 ku./ml), throughout the luteal phase of the oestrous cycle. Compared with the control ewes, this treatment significantly reduced pituitary and plasma FSH concentrations and increased the frequency and amplitude of the LH pulses, but did not affect pituitary LH concentrations. In a second experiment, five control and five bFF-treated ewes from experiment 1 were ovariectomized and the injection regime was altered to 2·5 ml s.c. every 8 h. This treatment was maintained for 21 days. In control ewes, plasma FSH concentrations rose significantly within 12 h and continued to rise for 3–4 days. Treatment with bFF abolished this increase and maintained plasma FSH concentrations below those observed in intact ewes. The rise in mean plasma LH concentrations evoked by ovariectomy was also partially inhibited in the bFF-treated ewes. The response to the gonadotrophin-releasing hormone (GnRH) agonist buserelin (5 μg i.v.) was measured 6, 12 and 18 days after ovariectomy. In control ewes the agonist consistently evoked large surges of both hormones but in bFF-treated ewes the FSH response was completely blocked and the initial phase of the LH response (the first 'pool') was greatly reduced. In experiment 3, six ewes were ovariectomized and passively immunized against GnRH 3 days after oestrus. The increase in plasma LH which normally follows ovariectomy was completely abolished and mean concentrations remained very low and did not change over the following 14 days. In contrast, mean FSH concentrations rose significantly within 12 h of ovariectomy and continued to rise until the third day, after which they fell gradually. Treating three of the ewes with bFF (2·5 ml s.c. every 8 h) 8 days after ovariectomy and immunization further reduced the FSH concentrations. When the ewes were injected repeatedly (200 ng i.v., hourly for 5 h) with [d - penicillamine - (But)6] - GnRH(1–9)nonapeptide ethylamide, a synthetic GnRH analogue which does not bind to the antiserum, there was a rapid rise in the secretion of LH in both control and bFF-treated animals but, as with the responses to buserelin, the initial response was significantly lower in bFF-treated than in control ewes. The concentrations of FSH rose after each injection in the control ewes but showed only a small response after the fourth and fifth injections in the bFF-treated ewes.

We conclude that bFF completely blocks the secretion of FSH in the acutely ovariectomized ewe by blocking the pituitary response to GnRH, an effect which is probably mediated, at least in part, by a reduction in the concentration of FSH in the gonadotrophs. The release of LH was only partially inhibited by bFF treatment and this effect was not related to pituitary LH concentrations. It seems that LH release is acutely controlled by hypothalamic stimulation and chronically controlled by ovarian feedback at the pituitary level whereas FSH release is controlled chronically by changes in hypothalamic stimulation and acutely by ovarian feedback on the anterior pituitary gland. Inhibin is an important component of this feedback on FSH release.

J. Endocr. (1986) 111, 287–296