Apparent absence of negative feedback in middle-aged persistent-estrous rats following luteinizing hormone-releasing hormone agonist treatment: relation to plasma inhibin and 17 beta-estradiol.

Abstract

Reproductive aging in female rats is associated with a transition from regular estrous cyclicity to an anovulatory condition described as persistent estrous (PE). This PE condition is characterized by continued follicular development with elevated circulating levels of estrogen and FSH. In an attempt to investigate further the age-related changes in neuroendocrine function of PE rats, we have developed a model through which the return of hypothalamic-pituitary and ovarian function can be assessed following the withdrawal of chronic LHRH agonist suppression. Subsequent to withdrawal of continuous (2.5 micrograms/h for 12 days) LHRH agonist [DTrp6, Pro9-NHEt]-LHRH (LHRH-AG) treatment, circulating FSH concentrations in PE rats increase and remain elevated with an apparent absence of ovarian negative feedback, and these rats fail to return to estrous cyclicity. In the present studies, estrogen administration induced significant decreases in FSH secretion in PE rats following withdrawal of LHRH-AG treatment and ovariectomy (OVX), suggesting that the negative feedback response to estrogen is maintained in PE females. However, progesterone administration 2 days later failed to elicit a positive feedback response of gonadotropin secretion in PE females prior to LHRH-AG treatment, serum inhibin and 17 beta-estradiol (E2) concentrations were similar in middle-aged PE rats and young cyclic females on proestrus, while FSH levels were significantly greater in PE rats. After withdrawal of LHRH-AG treatment, plasma FSH concentrations remained elevated in PE rats as compared to young rats despite similar increases in E2. However, increases in plasma inhibin were delayed and significantly attenuated in PE rats.(ABSTRACT TRUNCATED AT 250 WORDS)