Influence of Estradiol on NADPH Diaphorase/Neuronal Nitric Oxide Synthase Activity and Colocalization with Progesterone or Type II Glucocorticoid Receptors in Ovine Hypothalamus

• Published in: Biology of reproduction Vol. 67; no. 3; pp. 829 - 836
• Main Authors: DUFOURNY, Laurence, SKINNER, Donal C
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-09-2002
• Subjects: Animals; Arcuate Nucleus of Hypothalamus - chemistry; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - enzymology; Biological and medical sciences; Cell Count; Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Gonadotropin-Releasing Hormone - metabolism; Hormones and neuropeptides. Regulation; Hypothalamus - chemistry; Hypothalamus - drug effects; Hypothalamus - enzymology; Hypothalamus. Hypophysis. Epiphysis. Urophysis; NADPH Dehydrogenase - analysis; NADPH Dehydrogenase - metabolism; Neurons - chemistry; Neurons - drug effects; Neurons - enzymology; Nitric Oxide Synthase - analysis; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; Preoptic Area - chemistry; Preoptic Area - drug effects; Preoptic Area - enzymology; Receptors, Glucocorticoid - analysis; Receptors, Progesterone - analysis; Sheep; Tissue Distribution; Vertebrates: endocrinology; EC 1.14.13.39; Enzyme; Central nervous system; Estrogen; 17β-Estradiol; Hypothalamus; Progesterone receptor; NADPH dehydrogenase; Ovarian hormone; Nitric-oxide synthase; EC 1.6.99.1; Vertebrata; Mammalia; Enzymatic activity; Glucocorticoid receptor; Sheep; Artiodactyla; Oxidoreductases; Localization; Ungulata; Brain (vertebrata)
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.102.004648

Nitric oxide (NO) has been shown to play an important role in both the neuroendocrine reproductive and stress axes, which
are closely linked. Because progesterone (P 4 ) receptors (PRs) and glucocorticoid receptors (GRs) are not found in GnRH neurons and the NOergic system has been implicated
in the control of GnRH secretion, this study aimed to ascertain whether steroids altered the NOergic system. Our first objective
was to map the distribution of NO synthase (NOS) cells in the ovine preoptic area (POA) and hypothalamus and to determine
whether NOS activity is enhanced by estradiol (E 2 ) treatment. Using NADPH diaphorase (NADPHd) histochemistry, we found that NADPHd-positive neurons were spread throughout
the ovine POA and hypothalamus, and that all NADPHd cells were immunoreactive for NOS. In response to estradiol, a significant
increase in the number of NADPHd cells was noted only in the ventrolateral region of the ventromedial nucleus (VMNvl), with
no significant difference in the POA or arcuate nucleus. Progesterone and glucocorticoid receptors were colocalized with NADPHd
reactive neurons in the POA, arcuate nucleus, and VMNvl of ewes in both treatment groups. In ewes receiving estradiol, the
number of NADPHd-positive cells containing steroid receptors in the POA (PR, 81%; GR, 79%) and arcuate nucleus (PR, 89%; GR,
84%) was similar, but in the VMNvl, fewer NADPHd-positive cells contained GR (PR, 88%, GR, 31%). These data show that estradiol
up-regulates NOS activity in a site-specific manner and that the influence and possible interaction of progesterone and corticosteroids
on NO producing cells may differ according to the neural location.