The effect of neonatal thymectomy on gonadotropin secretion in the female rat

Abstract

The thymoprivic condition in the neonatally thymectomized or nude female mouse is accompanied by changes in estrous cyclicity, ovarian development and gonadotropin secretion. In the present studies, the neonatally thymectonized female rat was utilized to further investigate the nature of these changes in an attempt to clarify the role of the thymus in reproductive endocrine function. Two day old female Sprague-Dawley pups were thymectomized (TX) or sham thymectomized (STX) under anesthesia by hypothermia and allowed to recover under the care of their dams. Following vaginal opening at approximately 31-32 days of age, both TX and STX rats showed (100) normal estrous cyclicity. However, a high percentage of mature TX rats (37%) had inconsistencies in cycling, characterized by diestrous stages of lengths varying from 1-7 days. Some adult TX rats 100-150 days of age (41.6%) developed a borderline syndrome of ovarian dysgenesis termed "follicular dysgenesis" consisting of reductions in the numbers of corpora lutea growing and mature and enhanced follicular atresia. To determine whether the pituitary of the TX rat was functionally intact, plasma luteinizing hormone (LH) levels were measured by radioimmunoassay following the administration of synthetic luteinizing hormone releasing hormone (LHRH). Thymectomized rats released consistently and significantly greater amounts of LH than their sham operated littermates in response to 100 ng intravenously administered LHRH, a difference that was significant at the p < 0.01 or p < 0.005 levels (Student's t test). The possibility that the pituitary of the athymic rodent overresponds to hormonal stimulation is supported by these findings and by data derived from a second experiment in which TX rats released greater quantities of LH in response to estradiol positive feedback stimulation than STX rats. No differences were found in the LH response to ovariectomy in the TX and STX animals, implying that the negative feedback mechanism is intact and operating normally in the TX rodent. The data support a hypothalamic primary site of thymic influence functioning during a strictly defined neonatal critical period and suggest that removal of the thymus during this period results in a lesion of the tuberal and possibly the preoptic areas.