Estradiol and progesterone modulate the nitric oxide/cyclic gmp pathway in the hypothalamus of female rats and in GT1-1 cells.
Considerable evidence suggests that the nitric oxide (NO)/cGMP signaling pathway plays an important role in the expression of reproductive behavior and in gonadotropin-releasing hormone (GnRH) release from the hypothalamus The effects of the NO/cGMP pathway on GnRH release and gene expression have also been examined in GT1 cells. However, it is still controversial whether NO/cGMP signaling facilitates or inhibits GnRH release in these cells. The current study examined the effects of estradiol and progesterone on neuronal NO synthase (nNOS), soluble guanylyl cyclase (sGC), and NO-dependent cGMP production in the preoptic area (POA) and hypothalamus (HYP) as well as in GT1-1 cells. Ovariectomized female rats received vehicle, estradiol benzoate (48 h) and/or progesterone (3-4 h) before preparation of brain slices. GT1-1 cells were incubated with vehicle, estradiol (48 h), progesterone (3-4 h), or with both hormones. The combination of estradiol and progesterone increased the expression of nNOS protein in the POA and HYP. Hormones had little effect on the abundance of sGC. Estradiol and progesterone together greatly enhanced NO-stimulated sGC activity in HYP-POA slices. In GT1-1 cells, NO-stimulated sGC activity was significantly increased by estradiol and progesterone, alone or in combination, but sGC expression was not altered by hormones.
Chu
Hsiao-Pai
HP
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA.
Sarkar
Gayatri
G
Etgen
Anne M
AM
D000818:Animals; D002460:Cell Line; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D009599:Nitroprusside; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP