Expression of estrogen receptor-alpha and c-Fos in adrenergic neurons of the female rat during the steroid-induced LH surge.

Epinephrine is an important neurotransmitter that is synthesized in relatively few neurons of the medullary regions C1-C3. Epinephrine is involved, among others in the control of most neuroendocrine systems, such as corticotropin releasing hormone-, gonadotropin releasing hormone- and oxytocin/vasopressin-containing neurons as part of complex feedback loop systems that often include interactions with the gonadal or adrenal steroid hormones. In order to determine if the interactions between gonadal steroid hormones with the adrenergic neurons are direct or involve steroid-receptive interneurons that in turn innervate the adrenergic neurons, dual immunohistochemistry was applied to identify if estrogen receptor-alpha (ERalpha) protein was expressed by adrenergic, phenylethanolamine-N-methyl transferase (PNMT)-positive neurons and if estradiol can activate these neurons as determined by the transient expression of the transcription factor c-Fos. The results show that an average of 22% of all PNMT neurons in the C1 region, 38% in C2 and 42% in the C3 region express estrogen receptor-alpha protein with the highest numbers of dual labeled neurons in the central levels of the C1-C3 regions. Overall, the percentages of dual labeled PNMT/ERalpha neurons did not change during the steroid-induced LH surge. In contrast, the percentage of c-Fos expressing PNMT neurons changed significantly during the LH surge. Thus, c-Fos immunoreactivity was highest in all three regions at 1200 h with 69% of the PNMT neurons in C1, 60% in C2 and 79% in C3 co-expressing c-Fos. C-Fos expression was lowest before and after the surge with 39% of the PNMT neurons in the C2 region containing c-Fos at 0800 h, 52% c-Fos-positive PNMT neurons in C1 and 54% in area C3. The results show that many adrenergic neurons are direct targets for estradiol and that most PNMT neurons in the brainstem are activated during the initiation of the steroid-induced LH surge which suggests that epinephrine is one of the triggers that stimulates GnRH release during the surge.