Central injection of senktide, an NK3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of Fos expression in the rat hypothalamus

Arcuate neurokinin B (NKB) neurons express estrogen receptor-alpha and are strongly modulated by gonadal steroids. Although numerous studies suggest that NKB neurons participate in the reproductive axis, there is no information on the regulation of luteinizing hormone (LH) secretion by NKB or its receptor, NK3. In the present study, we determined if central injection of senktide, a selective NK3 receptor agonist, would alter serum LH in ovariectomized, estrogen-primed rats. The effects of senktide were compared to neuropeptide Y (NPY), a well characterized modulator of LH secretion. Saline, senktide, or NPY was injected into the lateral ventricle of unanesthetized rats and serial blood samples were collected for LH radioimmunoassay. The rats were sacrificed 90 min after injection and the brains were removed and processed for Fos immunocytochemistry. A significant inhibition of serum LH was observed from 30 to 90 min after injection of senktide relative to saline controls. In the senktide-injected rats, the inhibition of serum LH was accompanied by increased Fos expression in the medial preoptic area and arcuate nucleus-two reproductive control centers. Senktide also induced Fos in the paraventricular nuclei (PVN) and supraoptic nuclei (SON). Injection of NPY also inhibited serum LH but increased Fos expression only in the PVN and SON. This study provides the first demonstration of alterations in LH secretion by an NK3 receptor agonist. These data, combined with the induction of Fos in medial preoptic and arcuate neurons, strongly support the hypothesis that NKB neurons play a role in the regulation of gonadotropin secretion. (C) 2004 Elsevier B.V. All rights reserved.