Gonadotropin responsiveness to estrogens and low-level progesterone in the ovariectomized rhesus monkey

Abstract

When estrogen is administered to gonadectomized rhesus monkeys in sufficient quantity, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are initially suppressed and gonadotropin secretion is subsequently augmented. This study was designed to examine the ability of various orally administered estrogens to elicit biphasic pituitary responses in adult castrate rhesus monkeys and to investigate the role of low-level progesterone in altering these responses. In an incomplete block design, 13 treatments were constructed: (E2): 0.5, 5.0, 50 ?g/kg; (DES): 0.05, 0.5, 5.0 ?g/kg; zearalenone (Z): 10, 100, 1000 ?g/kg; or oil vehicle, each combined with progesterone. The remaining treatments (5.0, 0.5, and 100 ?g/kg of E2, DES, and Z, respectively) did not include progesterone. During six intervals, E2, DES, or Z was administered orally on Days 1, 2, and 3 and blood was sampled on Days 0, 3, and 8 of each period. A main effect of estrogen treatment was observed for LH and FSH secretion on Day 3 but not Day 8. There was no main effect of progesterone alone on release of either LH or FSH on days 3 or 8, nor were significant carry-over effects of progesterone, E2, DES, or Z on LH or FSH concentration apparent by Day 8 of any treatment. However, progesterone synergized with E2 to suppress Day 3 LH levels. Conversely, DES and Z interacted with progesterone to facilitate LH secretion at this time. FSH was not altered by the combination of progesteron and E2, DES, or Z but was dose-dependently influenced by estrogen alone, with maximally suppressive effects on Day 3 occurring at the high dose level of E2, DES, and Z. We have demonstrated a fundamental animal bioassay model that, in addition to existing models, might be used to monitor and predict the physiologic consequences of human exposure to estrogenic compounds from the food chain. These data also indicate that low blood levels of progesterone may synergize with estrogens to selectively stabilize estrogen-induced pituitary responses.