Porcine Follicular Fluid Contains Both Follicle- Stimulating Hormone Agonist and Antagonist Activities*

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Abstract
Several fractions were prepared from porcine follicular fluid, each having FSH receptor binding inhibitory activity. All were soluble in acidic acetone (pH 3.5) and insoluble in ether (pH 10.5), and could be separated on the basis of charge, using anion exchange HPLC. The effect of these fractions on aromatization of androstenedione to estradiol (basal levels or FSH stimulated) was studied in vitro using Sertoli cells from immature rat testes. Agonist activity, defined as the ability to stimulate secretion of estradiol in the absence of FSH, was present in one fraction weakly retained by the anion exchange column but eluted with a linear gradient between 0.2 and 0.5 M acetate, pH 5.0. In addition to agonist activity, this fraction inhibited binding of [125I]human (h) FSH to hFSH antiserum and to receptor. Another fraction with FSH binding inhibitory activity was more strongly retained by the anion exchange HPLC column and was eluted with 1.0 M acetate, pH 3.0. This fraction demonstrated antagonist activity, as defined by its ability to inhibit FSH-stimulated, but not basal, conversion of androstenedione to estradiol in vitro. Although it inhibited [125I]hFSH binding to receptor, no immunoreactivity could be demonstrated in this fraction. These observations demonstrate that inhibition of [125I]hFSH binding to receptor can reflect either agonist or antagonist activity, and that the latter activities are present in separate and distinct fractions derived from porcine follicular fluid.

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