Nitric oxide synthase in the guinea pig preoptic area and hypothalamus: Distribution, effect of estrogen, and colocalization with progesterone receptor

Nitric oxide (NO) may function as an intercellular messenger in the hypotha lamus and may play a role in the control of gonadotropin-releasing hormone (GnRH) secretion and sexual behavior. Progesterone also plays an important role in the regulation of reproductive functions. Recent experiments have s hown that progesterone-induced sexual behavior in ovariectomized, estrogen- primed rats was caused by the release of NO from nitric oxide synthase (NOS )-containing neurons and the subsequent stimulation of the release of GnRH. To provide further neuroanatomical support for the role of NO in these gon adal steroid-dependent behavioral and physiological processes, we determine d (1) the distribution of the nicotinamide-adenosine-dinucleotide phosphate -diaphorase (NADPHd) and NOS enzymes in the guinea pig preoptic area and hy pothalamus, regions that contain steroid receptors; (2) the effect of estro gen on NADPHd activity in these regions; and (3) the neuroanatomical relati onship between NOS and the progesterone receptor (PR). For this purpose, si ngle(NADPHd) and double- (NADPHd with NOS or NADPHd with PR or NOS with PR) staining techniques were applied to sections of brains of guinea pigs. The studies showed scattered NADPHd-positive neurons in most parts of the preo ptic area and heavily stained cells in the hypothalamus. In these regions, the pattern and density of NOS immunoreactivity closely corresponded to the pattern of NADPHd staining. Quantitative analysis showed an increase in th e number of NADPHd-positive neurons in the ventrolateral nucleus of ovariec tomized animals primed with estradiol. Approximately 16% of the NOS-immunor eactive (IR) cells in the rostral preoptic area and 55% of NOS-IR cells in the ventrolateral nucleus displayed PR immunoreactivity. These results sugg est that NOS may be regulated by gonadal steroids and provide neuroanatomic al evidence that progesterone may exert its effect directly on more than ha lf of NOS-synthesizing cells in the ventrolateral nucleus, a key region in the control of sexual behavior. J. Comp. Neurol. 407:207-227, 1999. (C) 199 9 Wiley-Liss, Inc.