Effects of age on beta 1- and beta 2-adrenergic receptors in the brain assessed by quantitative autoradiography

Aging female rats undergo a loss of reproductive cyclicity that has been correlated with alterations in norepinephrine neuronal activity in specific hypothalamic regions involved in the regulation of gonadotropin secretion. We explored the possibility that deteriorating reproductive function may also be due to changes in the density of receptors which bind and mediate responsiveness to norepinephrine. Existing evidence suggests that beta-adrenergic receptors mediate norepinephrine's inhibitory effect on luteinizing hormone (LH). Therefore, we determined whether changes in beta-adrenergic receptor densities occur in specific hypothalamic nuclei associated with reproductive function. Furthermore, we wished to determine whether age affects beta 1- and beta 2-adrenergic receptor densities differentially and whether age-related changes in receptor densities are related to hormonal status and/or vaginal smear cytology of the animals. Old constant estrous rats, old persistent diestrous rats, young cycling rats on estrus, and young cycling rats on diestrus were killed at 1000 h and brain beta 1- and beta 2-adrenergic receptor densities were measured using topical autoradiographic and computerized image analysis methods which permit a high level of neuroanatomical discrimination. We analyzed beta 1- and beta 2-adrenergic receptor densities in 7 brain areas including 4 hypothalamic regions known to be important in reproductive function. The pineal gland, the molecular layer of the cerebellum and the caudate putamen were examined because they contain high concentrations of beta-adrenergic receptors which have been reported to change with age. Serum luteinizing hormone was measured in the same rats. Serum LH concentrations were the same in all rats regardless of vaginal smear cytology and age.(ABSTRACT TRUNCATED AT 250 WORDS)