Medical outcome data and physician feedback: walls are coming down!

Physician study groups or task forces based at the local or state level can play an important role in monitoring and disseminating outcome data. Twelve states already have begun pilot projects to look at data on practice variations.     

Direct inhibitory effect of estrogen on LH-stimulated androgen synthesis by ovarian cells cultured in defined medium

The direct inhibitory effect of estrogen on ovarian androgen synthesis was investigated. When primary cultures of rat ovarian theca-interstitial cells were grown in defined medium with LH there was a marked increase in androgen synthesis of which 98% was androsterone (control = 11 ± 2 ng; LH = 1219±217 ng/ml/10⁶ cells). Diethylstilbestrol (DES), estrone (E₁), estradiol (E₂), and estriol (E₃) inhibited LH-stimulated androsterone synthesis by 81%, 81%, 81%, and 47%, respectively. The ED₅₀'s of the estrogens were: DES = 4.2±2.l × 10^?9M; E₁ = E₂ = 9.5±2.4 × 10^?8 M; and E₃ = 3.8±2.6 × 10^?7 M. The estrogen effect was very rapid ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ = 10 min) and long-lasting. Metabolic studies revealed that estrogen inhibited androsterone, androstenedione, 5α-androstane-3α, 17β-diol, and testosterone accumulation by 80%, dehydroepiandrosterone and 17α-hydroxypregnenolone by 40%, 17α-hydroxyprogesterone by 30%, while pregnenolone and progesterone were unchanged. These results prove, for the first time, that estrogen can directly inhibit LH-stimulated androgen production in ovarian theca-interstitial cells and suggest that mechanism involves, at least in part, a rapid selective inhibition of the 17α-hydroxylase/C_17–20 desmolase activities.     

A monoclonal antibody recognizes a 39 kDa protein expressed in atretic granulosa cells

A major problem in ovarian physiology is the lack of conveniently quantifiable markers of atresia. Towards this end, we identified a monoclonal antibody (anti-OA-2) that selectively recognizes granulosa cells in atretic follicles. When cryostat sections of rat ovaries were incubated with anti-OA-2, granulosa cells in atretic follicles showed intense immunofluorescent labeling. In contrast, no anti-OA-2 immunoreactivity was observed in the granulosa of the healthy follicles. The amount of anti-OA-2 binding was significantly enhanced when atresia was stimulated by treatment with human chorionic gonadotropin, testosterone, or estrogen withdrawal. The results of immunoprecipitation and Western blot analyses indicated that the OA-2 antigen is a 39 kDa protein which is actively synthesized by the granulosa during atresia. The 39 kDa protein is localized at or near the inner surface of the plasma membrane. We conclude that the anti-OA-2 monoclonal will prove useful as a convenient analytical tool to study the regulation of granulosa atresia.     

Inhibin A, inhibin B and activin A concentrations in follicular fluid from women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by arrestedfollicle development at the early antral stage. Alterationsin inhibin production by developing follicles could be involvedin PCOS by suppressing follicle stimulating hormone concentrationsduring the follicular phase of the menstrual cycle as well asby increasing thecal androgen production. Inhibin B appearsto be more important than inhibin A during the follicular phase;however, there are no data regarding the follicular fluid concentrationsof inhibin B in PCOS. The purpose of this study was to compareinhibin A, inhibin B and activin A concentrations in the follicularfluid from regularly cycling women and women with PCOS. InhibinA, inhibin B and activin A were measured in the follicular fluidof 4–7 mm follicles from PCOS ovaries and size-matchedfollicles from normally cycling women by specific and sensitivetwo-site enzyme-linked immunosorbent assays. In both controland polycystic ovaries, inhibin B was approximately 10-foldhigher than activin A and more than 100-fold higher than inhibinA. There was no difference in activin A concentrations betweenPCOS and control follicles. In control ovaries, the inhibinB and inhibin A concentrations in dominant follicles were significantlyhigher than in cohort follicles. While inhibin A concentrationswere lower in PCOS follicles than in normal cohort follicles,there was no difference in inhibin B concentrations betweenPCOS follicles and normal cohort follicles. These data are consistentwith the concept that inhibin B is the physiologically mostimportant form of inhibin during the follicular phase of themenstrual cycle and indicate that PCOS is not associated withincreased inhibin B concentrations in follicular fluid.