ABSTRACT

The potential direct ovarian effects of immunoneutralization of inhibin, which increases, and follicular fluid treatment, which inhibits, follicle development in normal ewes was investigated in a sheep model in which endogenous FSH and LH secretion was suppressed thus removing any potential effects of treatment-induced alterations in endogenous FSH or LH secretion. Eighteen Welsh Mountain ewes were treated with two agonist implants containing 3·3 mg buserelin giving a total of 6·6 mg buserelin per animal. During week 5 of treatment all ewes were given a 72-h continuous infusion of ovine FSH (5 μg/h) starting at 09.00 h. Six ewes were treated with antiserum to the 1–26α peptide fragment of porcine inhibin 0 h and 24 h after the start of the FSH infusion, and a further six ewes were treated with charcoal-stripped ovine follicular fluid (oFF) as a source of inhibin, at 09.00 and 17.00 h throughout the 72 h of FSH infusion.

The plasma concentrations of both FSH and LH were significantly reduced in all ewes after 5 weeks of treatment with buserelin, and no large follicles > 2·5 mm in diameter were present. Treatment with inhibin antiserum or oFF had no effect, compared with control ewes, on the plasma concentrations of either FSH or LH during the FSH infusion period. After 72 h of FSH infusion there was no difference in the number of small follicles (<2·5 mm in diameter) or large follicles (> 2·5 mm in diameter) or the size of the largest follicles between control ewes and ewes treated with either inhibin antiserum or oFF. However, large oestrogenic follicles from ewes treated with oFF secreted significantly (P<0·01) more testosterone in vitro and had a significantly (P<0·01) higher follicular fluid concentration of testosterone than both control ewes and ewes treated with inhibin antiserum.

These results show that the effects of inhibin immunization in increasing follicle growth and oFF in inhibiting follicle growth in normal sheep are not related to a direct effect of these treatments on the ovary, but are mediated by the effects of treatment on the plasma concentrations of FSH. The effect of oFF in increasing thecal androgen production suggests an increase in thecal sensitivity to LH. In the sheep model used in the present study, pulsatile LH secretion was abolished and large follicles were induced to develop under the influence of FSH in the presence of only basal concentrations of LH. The results suggest a potential interaction between oFF components and pulsatile LH secretion in modulating FSH-induced preovulatory follicle growth through an alteration in thecal sensitivity to LH.

Journal of Endocrinology (1991) 131, 401–409