Our overall objective is to characterize and understand the events that occur in the human central nervous system in response to the ovarian failure of menopause. An equally important goal is to contribute to our understanding of the neuroendocrine mechanisms that regulate reproduction. Although complex, the neural basis of reproductive function is amenable to experimentation because of the known feedback circuits. Control mechanisms can be studied at many different levels, ranging from plasma hormone levels, to gene expression in subsets of hypothalamic neurons.
We have described dramatic changes in neuronal morphology and neuropeptide gene expression in the hypothalamus of postmenopausal women. Neurokinin B and kisspeptin gene expression is markedly increased in the infundibular nucleus of postmenopausal women, along with hypertrophy of these neurons. We have hypothesized that the hypertrophied neurons participate in the sex-steroid feedback on gonadotropin secretion. Molecular, pharmacological and anatomical approaches using animal models have been conducted to test this hypothesis. The significance of these studies is underscored by the recent demonstration in other laboratories that mutations in the gene encoding NKB or its receptor leads to loss of pubertal development and infertility in humans.
More recently, we have initiated basic studies on the effects of estrogen on hypothalamic thermoregulation. Our goal is to relate the changes that occur in the postmenopausal human hypothalamus to the dramatic changes in hypothalamic thermoregulation known as hot flushes.