PROGESTERONE PRODUCTION BY MONKEY LUTEAL CELL SUBPOPULATIONS AT DIFFERENT STAGES OF THE MENSTRUAL-CYCLE - CHANGES IN AGONIST RESPONSIVENESS

Small (less-than-or-equal-to-15 mu-m diameter) and large (< 20 mu-m diam.) luteal cells of the rhesus monkey have been separated by flow cytometry based on light scatter properties. To determine whether the steroidogenic ability and agonist responsiveness of luteal cell sub-populations vary during the life span of the corpus luteum, small and large cells were obtained at early (Days 3-5), mid (Days 7-8), mid-late (Days 11-12), and late (Days 14-15) luteal phase of the cycle. Cells (n = 4 exp./group) were incubated in Ham's F-10 medium + 0.1% BSA for 3 h at 37-degrees-C with or without hCG (100 ng/ml), prostaglandin E2 (PGE2; 14 mu-M), dibutyryl-cAMP (db-cAMP; 5 mM), or pregnenolone (1 mu-M). Basal progesterone (P) production by large cells was up to 30-fold that by small cells depending on the stage of the cycle. HCG stimulated (p < 0.05) P secretion by both small (1.8 +/- 0.2-fold) and large (3.7 +/- 0.7-fold) cells in the early luteal phase. HCG responsiveness declined during the luteal lifespan; P production by small cells was not significantly enhanced by hCG by mid luteal phase, whereas that by large cells was stimulated 1.7 +/- 0.2-fold (p < 0.05) even at late luteal phase. Cell responses to db-cAMP were similar to those for hCG. PGE2 increased P production by small (2.0 +/- 0.2-fold) and large (3.6 +/- 0.7-fold) cells in the early luteal phase; by mid luteal phase, only large cells responded, and no stimulation by PGE2 occurred at subsequent stages. Large cells exhibited a greater capacity than small cells to convert pregnenolone to P, but relative stimulation (up to 42-fold) was greater in small cells. A progressive decline in steroidogenic cell density and in large:small cell ratio was observed in dispersed cell preparations with advancing age of the corpus luteum. Thus, (1) large cells from the primate corpus luteum are more acutely responsive to gonadotropin and PGE2 than are small cells and (2) differential changes in sensitivity to agonists acting via cAMP-mediated pathways, together with demographic changes in small and large cell subpopulations, may influence the function of the corpus luteum during the progression of the luteal phase of the menstrual cycle.