ANDROGEN PRODUCTION BY MONKEY LUTEAL CELL SUBPOPULATIONS AT DIFFERENTSTAGES OF THE MENSTRUAL-CYCLE

Androgens produced by the primate corpus luteum (CL) serve as precurso rs for estrogen synthesis; moreover, detection of androgen receptors i n luteal tissue suggests a regulatory role within the CL. To determine the cellular source(s) and agonist regulation of androgen production during the lifespan of the primate CL, luteal tissues were collected h om rhesus monkeys in the early (days 3-5 post-LH surge), mid (days 7-8 ), mid-late (days 11-12), and late (days 14-15) luteal phase of the me nstrual cycle. Collagenase-dispersed cells (i.e. mixed cells) were ana lyzed by flow cytometry based on light scatter properties and sorted i nto populations of small (less than or equal to 15 mu m) and large (>2 0 mu m) luteal cells. Cells (n = 4 animals/stage) were incubated in Ha m's F-10 and 0.1% BSA for 3 h at 37 C with or without hCG (100 ng/mL), PGE(2) (14 mu mol/L), or dibutyryl cAMP (dbcAMP; 5 mmol/L), and andro stenedione (A(4)) and testosterone were measured. Basal A(4) productio n by large cells was markedly higher (P < 0.05) than that by small cel ls (e.g. mid-late luteal phase, 821 +/- 188 vs. 69 +/- 25 pg/mL . 5 x 10(4) cells/3 h; mean +/- SEM), whereas that by mixed cells was interm ediate (317 +/- 205 pg/mL). In the early luteal phase, hCG stimulated A, synthesis by mixed (1.6-fold; P < 0.05) and large (3.1-fold; P < 0. 05) luteal cells, but not by small cells (1.3-fold); By the mid-late l uteal phase, hCG did not increase A(4) production by any cell type, al though hCG responsiveness returned to large cells (2.0-fold increase; P < 0.05) by the late luteal phase. PGE(2) responsiveness by cell type s was similar to that of hCG, except large cell responsiveness did not return in the late luteal phase. In all cell types, dbcAMP stimulated the largest increase in A(4) levels; in the mid-late luteal phase, sm all and large cells responded to dbcAMP with 8.2- and 3.0-fold increas es (P < 0.05) in A(4) production, respectively. When luteal cells were incubated with the steroidogenic substrates, 17 alpha-hydroxyprogeste rone or 17 alpha-hydroxypregnenolone (1 mu mol/L), large cells produce d much more (P < 0.05) A(4), testosterone, estrone, and estradiol than small cells. Both substrates elicited similar patterns of androgen pr oduction, with A(4) synthesis predominant in all luteal cell types. Th us, cell subpopulations in the primate CL can be distinguished by thei r ability to produce androgen and estrogen. Changes in agonist-respons ive androgen production may influence the local steroid milieu and fun ction of the CL during the menstrual cycle.