Hypothalamic alterations and reproductive aging in female rats: Evidence of altered luteinizing hormone-releasing hormone neuronal function

Prior to the age-related loss of regular estrous cycles, female rats exhibi t an attenuated preovulatory LH surge, a sign that reproductive decline is imminent. Numerous studies have revealed an important role for the hypothal amus in aging of the reproductive axis in this species. Because LHRH repres ents the primary hypothalamic signal that regulates gonadotropin release, a ssessments of LHRH neuronal activity can provide a window into hypothalamic function during reproductive aging. Studies of the dynamic activity of LHR H neurons during times of enhanced secretion have revealed deficits in midd le-aged females. Available data are consistent with a decline in LHRH synth esis, transport, and secretion in middle-aged females during times of incre ased demand for LHRH output. Moreover, the alterations noted in LHRH neuron al function could account, in part, for the attenuation and eventual loss o f the preovulatory LH surge with age. Elements extrinsic to LHRH neurons un doubtedly contribute to the decline in the parameters of LHRH neuronal func tion observed in middle-aged females. Whether alterations intrinsic to LHRH neurons also play a role in the age-associated reduction in LHRH synthesis and secretion remains to be determined. Recent examinations of hormone pro files during the perimenopausal period suggest that a potential hypothalami c contribution to aging of the reproductive axis in women warrants further examination.