Blockade of progesterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine.

The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.