Enlarging Effects of Estradiol on the Nuclear Volume of Neurons in the Hypothalamus during Aging

Abstract

Neuronal nuclear volumes (NNVs) were measured in the medial preoptic nucleus (MPN), anterior hypothalamic area (AHA) and arcuate nucleus (ARN) of young adult, middle-aged, and old rats of both sexes. The NNVs in the darkly stained sexual-dimorphic nucleus of the preoptic area (SDN-POA) and the lighter staining surrounding area (non-SDN-POA) within the MPN were measured separately. Intact young and middle-aged female rats had larger NNVs than those of the males in SDN-POA, non-SDN-POA and AHA but not in ARN. During aging, only intact old female rats manifested significant NNV shrinkage in all the measured areas. Long-term treatment with estradiol benzoate (EB) caused a significant enlargement of the NNVs in non-SDN-POA and ARN of middle-aged and old male rats as well as the NNVs in SDN-POA, non-SDN-POA and ARN of old female rats. The enlarging effect of EB on NNVs in both SDN-POA and non-SDN-POA of female rats could be prevented by ovariectomy. Furthermore, NNVs in SDN-POA and non-SDN-POA of ovariectomized female rats were even smaller than those of the age-matched intact female rats. These results indicate that: (1) the NNVs of MPN and ARN in male and female rats were enlarged after long-term exposure of physiological dose of estradiol; (2) the enlarging effects of EB on NNV in MPN can explain why the NNV of intact female rats is larger than that of males, and (3) during aging, the sex-specific shrinkage of NNVs in MPN, AHA and ARN of female rats may be due to an intrinsic aging process rather than long-term effects of EB.