title: 3 beta-hydroxysteroid dehydrogenase inhibitor reduces ovarian steroid production but increases ovulation rate in the ewe: interactions with gonadotrophins and inhibin.
abstract: Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles greater than 6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion.
authors.affiliation: AFRC Institute of Animal Physiology and Genetics Research, Edinburgh Research Station, Roslin, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Webb
authors.forename: G
authors.initials: G
authors.lastname: Baxter
authors.forename: D
authors.initials: D
authors.lastname: McBride
authors.forename: A S
authors.initials: AS
authors.lastname: McNeilly
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D007265:Inhibins / Q000096:biosynthesis / Q000097:blood; D007986:Luteinizing Hormone / Q000096:biosynthesis / Q000097:blood; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000378:metabolism*; D010060:Ovulation / Q000187:drug effects*; D012756:Sheep / Q000378:metabolism*
chemical_list: D000737:Androstenols; D012739:Gonadal Steroid Hormones; D007265:Inhibins; C046855:epostane; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases