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DELAYED RESPONSE TO ESTRADIOL POSITIVE FEEDBACK AFTER PRENATAL EXPOSURE TO TESTOSTERONE IN THE FEMALE SHEEP.
Sharma, Tejinder1, Herkimer, Carol1, Foster, Douglas 1, Robinson, Jane2, Padmanabhan, Vasantha1, 1 2
ABSTRACT- Prenatal exposure of sheep to testosterone disrupts ovarian cyclicity, and leads to multicystic ovaries and anovulation later in adulthood. Because failure of the LH surge mechanism is the potential cause for anovulation in the cystic cow (Res. Vet. Sci. 51:180, 1991), we determined if the LH surge mechanism is compromised in the androgenized ewe. In Experiment 1, we compared the positive feedback responses of prenatally androgenized (days 60-90 days, n=13 or 30-90 days, n=3) and normal (n=10) adult ewes to estradiol (E 2) during the first non-breeding season. A surge-inducing dose of E 2 was provided by 4 (3-cm) implants. Jugular blood was sampled every 2 h starting 4 h before through 72 h after E 2. In controls, the LH surge began at 15.4 ± 1.19 h. It was progressively delayed in the 60-90 day (21.4 ± 1.3 h) and 30-90 day androgenized ewes (27 ± 1.0 h). Experiment 2 determined if progesterone (P) pretreatment could overcome the defect in the LH surge generating system as in cystic cows (Res Vet Sci 51:180, 1991). A subset of above control (n=6) and prenatally androgenized ewes (60-90 days, n=8 and 30-90 days, n=3) were pretreated with P (two Controlled Internal Drug Releasing devices, CIDR) for 12 days. E 2 implants were inserted 16 h after P withdrawal. Relative to controls (surge onset, 23.3 ± 0.84 h), onset of LH surge was delayed only in the Day 30-90 (37 ± 1.0 h) but not the 60-90 group (25.2 ± 1.1 h). In both experiments, the amplitude of the LH surge was of the control in the Day 30-90 but not the Day 60-90 androgenized group. These findings raise the possibility that after early exposure to androgens development of the anovulatory condition in adulthood may stem from progressive deterioration of the surge generating system. (Supported by USPHS HD 23812 and a Parke Davis educational grant).
KEY WORDS: LH surge, cystic ovaries, prenatal androgenization, anovulation
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