Effect of an inhibitor of 3 beta-hydroxysteroid dehydrogenase on progesterone concentrations and embryo survival in sheep.
The effect of an inhibitor of 3 beta-hydroxysteroid dehydrogenase on peripheral progesterone concentration during the luteal phase of the oestrous cycle and on embryo survival was determined in sheep. Following administration of 10, 50, 100 or 250 mg epostane (4,5-epoxy-17-hydroxy-4,17,dimethyl-3-oxo-androstane-2-carbonitrile) progesterone concentrations were significantly lower than control levels 4 h after injection, from 2.5 to 22 h, 1.5 to 24 h and 1 to 24 h after injection respectively. There appeared to be no effect on peripheral oestradiol concentrations. Adrenal progesterone production was small and not influenced by epostane treatment. Epostane was administered on day 9 of the oestrous cycle to cause a reduction in progesterone concentrations for approximately 12-18 h on day 9 only (group 1, 250 mg epostane on day 9), or a series of such reductions on 3 consecutive days (group 2, 50 mg epostane on days 9, 10 and 11) or a continuous reduction for 3 days (group 3, 250 mg epostane on days 9, 10 and 11). The proportion of ewes that were pregnant was significantly (P less than 0.05) lower in ewes treated to give a continuously low progesterone concentration for 3 days than in either controls or ewes in which progesterone concentration was reduced for less than 24 h (in controls and groups 1, 2 and 3 the proportion was 85, 92, 54 and 18% of ewes treated respectively). Embryo survival was not affected by administration of 250 mg epostane on days 9, 10 and 11 if luteal phase levels of progesterone were maintained by insertion of a silicone elastomer implant of the steroid.(ABSTRACT TRUNCATED AT 250 WORDS)
Ashworth
C J
CJ
Wilmut
I
I
Springbett
A J
AJ
Webb
R
R
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D005260:Female; D008183:Luteal Phase; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep / Q000196:embryology*
D000737:Androstenols; D011374:Progesterone; C046855:epostane; D015096:3-Hydroxysteroid Dehydrogenases