Dynamics of progesterone and estrogen receptor alpha in the ventromedial hypothalamus

Cyclic fluctuations of estradiol and progesterone in females influence neuronal activity in the ventrolateral division of the ventromedial hypothalamic nucleus (VMNvl), through the activation of progesterone (PRs) and estrogen receptors (ERs). The expression of ER and PR in the VMNvl is influenced by their cognate ligands and is a central upstream trigger in the pathway of VMNvl-dependent modulation of endocrine responses. By studying the role played by estradiol and progesterone in PR and ERα expression in the VMNvl along the estrous cycle and how the two receptors interact in the same neuron, we aim at evaluate the synergistic action both ovarian hormones in the regulation of VMNvl activity. It was estimated, along the estrous cycle, the number of VMN neurons expressing PR or ERα, by stereological methods, and it was determined the percentage, and rostro-caudal distribution, of neurons simultaneously expressing both receptors. The highest number of PR- immunoreactive neurons was seen at Proestrus and of ERα-immunoreactive neurons was seen at Proestrus and Metestrus. The ERα/ PR co-localization is increased at caudal levels. About half the neurons expressing PR co-express ERα, a proportion that stays constant along the estrous cycle. The percentage of ERα neurons co-expressing PR changes from 60% at Proestrus to 40% at Metestrus. Fluctuations in circulating ovarian hormone levels promote coordinated changes in PR and ERα expression and co-localization. This may be an important mechanism in the regulation of input relayed by the VMNvl, allowing a precise modulation of endocrine responses.

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