Distribution of estrogen and progesterone receptors in the primate ovary, with emphasis on subpopulations of cells within the corpus luteum.

Abstract

Both estradiol and progeterone are proposed autocrine or paracrine regulators of ovarian function in primate species. However, specific receptors for these steroids have not been localized to individual compartments of the primate ovary. Using immunocytochemical techniques, estradiol receptors were detected in the germinal epithelium, but not other structures, of ovaries obtained from rhesus or cynomolgus monkeys during the follicular and luteal phases of the menstrual cycle. In contrast, progesterone receptors were present in stromal and interstitial tissue, the thecal layers of healthy and atretic follicles, as well as the functional corpus luteum. These results are consistent with the concept of a receptor-mediated role for progesterone, but not estrogen, within the predominant gametogenic and endocrine structures, e.g., the follicle and corpus luteum, of the primate ovary. The recent discovery of distinct cell types in the corpus luteum of domestic ungulates has revised concepts on the control of luteal function in these species. Studies were designed to test the hypothesis that the primate corpus luteum consists of cell subpopulations that differ in physical characteristics, function and regulation. Cells enzymatically-dispersed from the monkey corpus luteum at mid-luteal phase of the menstrual cycle differed in size (diameter) and the presence of the steroidogenic enzyme, 3β-hydroxysteroid dehydrogenase (3β-HSD). Analysis of dispersed cells for forward and 90° light scatter properties by flow cytometry revealed two distinct continua (Cα and Cβ). These continua were isolated using the sorting capabilities of the flow cytometer. Cα contained single cells of ≤ 15 μm and cell clusters; the cells were typically 3β-HSD-negative nonsteroidogenic. Cβ consisted of single cells that increased in size up to 40 μm and were 3β-HSD-positive. Cβ was divided into two regions (R₁ and R₃) and the cells isolated. R₁ cells were ≤ 15 μm whereas R₃ cells were ≥ 20 μm. Basal progesterone and estrogen production by R₃ cells was greater than that produced by R₁ cells (as determined by radioimmunoassay of the incubation media). Relative stimulation of progesterone production by hCG, cAMP or PGE₂ was not different between R₁ and R₃ luteal cells. These results support the hypothesis that the primate corpus luteum consists of distinct cell subpopulations which differ in size and steroidogenic capacity. However, the cell types which secrete progesterone are typically responsive to gonadotropin and PGE₂, possibly via a cAMP-mediated pathway.