Estrogen modulation of the alpha-1-adrenergic response of hypothalamic neurons

Intracellular recordings were made from 106 arcuate and cell-poor zone (ARC-CPZ) neurons in sagittal slices prepared from intact, ovariectomized and ovariectomized plus estradiol-benzoate-treated female guinea pigs, and the effects of norepinephrine (NE), the alpha 1-agonist methoxamine (MX) and the beta-agonist isoproterenol were tested. Either bath application or pressure application of 2-100 microM NE reversibly hyperpolarized and inhibited the spontaneous firing of the majority (57%, n = 60) of ARC-CPZ neurons. Isoproterenol also inhibited the majority (75%) of the ARC-CPZ neurons which it was tested on. In addition, 2-100 microM NE depolarized and/or increased the spontaneous activity of 20% (n = 21) of ARC-CPZ neurons, and some of these (n = 8) exhibited bursting activity. Similar doses of MX mimicked the NE excitation (depolarization and/or increased firing) in 48% (n = 14) of the ARC-CPZ neurons tested. Based on the serum levels of 17 beta-estradiol, the three groups of females were divided into high ( greater than 30 pg/ml) and low (less than 30 pg/ml) estrogen groups, and it was found that endogenous or exogenous estrogen significantly increased the number of neurons responding to MX (from 29 to 75%). Using intracellular labeling with procion yellow and immunocytochemistry, we have identified that luteinizing-hormone-releasing hormone neurons respond to NE. Therefore, it is suggested that one mechanism for an increase in the noradrenergic excitatory drive at the time of the preovulatory surge of luteinizing hormone in the mammal is an increase in the neuronal response to alpha 1-adrenergic stimulation.