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Modulation of Serum Follicle-Stimulating Hormone Bioactivity and Isoform Distribution by Estrogenic Steroids in Normal Women and in Gonadal Dysgenesis^*

Department of Pediatrics, Division of Pediatric Endocrinology, University of Michigan Ann Arbor, Michigan 48109

Address requests for reprints to: Dr. Padmanabhan, D 3252 Medical Professional Building, Department of Pediatrics, University of Michigan Hospitals, Ann Arbor, Michigan 48109-0781.

To determine the influence of estrogenic steroids on serum FSH bioactivity (B) and immunoreactivity (I) and the FSH isoform distribution profiles, we studied normal women during ovulatory menstrual cycles and a patient with gonadal dysgenesis treated with diethylstilbestrol (DES). Four women with ovulatory menstrual cycles, as judged from their serum immunoreactive LH, FSH, progesterone, and estradiol profiles in daily blood samples, had a significant increase in the mean FSH B/I ratio (P < 0.05) during the midcycle phase of their menstrual cycles. Similarly, in the patient with gonadal dysgenesis the FSH B/I ratio rose significantly (P < 0.05) after 3 weeks of DES treatment and declined during the posttreatment period. In five additional normal women, serum obtained during the follicular, midcycle, and luteal phases of their menstrual cycles was chromatofocused, and the FSH isoform distribution pattern determined. Sera obtained from the patient with gonadal dysgenesis before, during, and after DES administration were pooled and studied similarly. Chromatofocusing of a human pituitary tumor extract allowed for determination of the FSH B/I ratio in different pH ranges. The highest FSH B/I ratio was found in the more basic fractions (pH range 5.6–6.0) compared to the acidic fractions. During both the midcycle phase of the normal cycles and the DES administration period in the studies of the patient with gonadal dysgenesis, there was a shift of the FSH isoforms (as measured by immunoassay) to the basic pH range. In contrast, the mid- to late luteal phase samples, which had low B/I ratios, had an increase in FSH isoforms in the acidic pH range (<4.8). Similarly, in the patient with gonadal dysgenesis FSH isoforms in the basic range were more abundant during the DES treatment period than in the pre- or posttreatment serum pools. Therefore, it appears that endogenous and exogenous estrogenic stimulation alters FSH isoform distribution such that FSH isoforms that are more basic and have increased biological activity are secreted.

^* Presented in part at the American Physiological Society Meeting, New Orleans, LA, 1986, and the 69th Annual Meeting of The Endocrine Society, Indianapolis, IN, 1987. This work was supported by NIH Grant HD-18515 and biomedical support grants (to V.P. and I.Z.B).

Received February 5, 1988.

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