Effect of a nonsteroidal aromatase inhibitor on in vitro and in vivo secretion of estradiol and on the estrous cycle in ewes.
Three experiments were performed to study effects of decreased concentrations of estradiol-17 beta (E2) on lifespan and function of ensuing ovine corpora lutea (CL). In experiment 1, 52 follicles were collected from 10 ewes and placed into individual culture with 0 or .01 microCi 3H-androstenedione (10 ng; 3H-A) and 0, 10(-11), 10(-9), 10(-7), or 10(-5) M of a nonsteroidal aromatase inhibitor, CGS16949A (CGS). Concentrations of E2 secreted into the medium, and synthesis of estrogens as estimated by formation of 3H-water from 3H-A were decreased by 10(-5) and 10(-7) (P < .01), but not 10(-9) or 10(-11) M CGS. In experiment 2, luteolysis was induced in 24 ewes by injection of PGF2 alpha on days 5 to 10 of the estrous cycle (0 hr). Ewes received 0, 0.5, 1.0, 2.0 or 4.0 mg CGS per kg BW i.v. at -12, 0, 12 and 24 hr, and an ovulatory dose of hCG at 36 hr. Jugular (P < .001) and vena caval (P < .001) concentrations of E2 were decreased by CGS at all doses tested for 8 to 10 hr, but had returned to levels similar to control ewes by the time of the next injection. Concentrations of E2 around the time of the LH surge were similar in control and treated ewes. During the subsequent luteal phase, concentrations of progesterone (P4) were similar in control and treated ewes. Thus, transient decreases in E2 during the follicular phase were not deleterious to the subsequent luteal phase. In experiment 3, luteolysis was induced in 18 ewes by injection of PGF2 alpha on days 6 or 7 (0 hr) of the estrous cycle. Ewes received 0 or 1 mg CGS per kg BW i.v. every 8 hr from 0 to 40 hr. Ovulation was induced with hCG at 36 hr. CGS reduced jugular (P < .001) and vena caval (P < .001) concentrations of E2, prevented an endogenous surge of LH (P < .05) and increased (P < .001) concentrations of FSH. All ewes had ovulated a marked follicle by 72 hr, but onset of the luteal phase, as assessed by concentrations of P4, was delayed (P < .01) in ewes receiving CGS. Delayed luteal phases were not solely attributable to the presence of new CL or to luteinization of follicular cysts. When data were aligned according to the day ewes were observed in estrus, profiles of P4 did not differ with treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Benoit
A M
AM
West Virginia University, Morgantown.
Inskeep
E K
EK
Dailey
R A
RA
D000818:Animals; D047072:Aromatase Inhibitors; D046508:Culture Techniques; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism*; D004971:Estrus / Q000187:drug effects*; D017316:Fadrozole / Q000494:pharmacology*; D005260:Female; D008183:Luteal Phase / Q000187:drug effects / Q000502:physiology; D006080:Ovarian Follicle / Q000378:metabolism; D012756:Sheep / Q000502:physiology*
D047072:Aromatase Inhibitors; D004958:Estradiol; D017316:Fadrozole