Cyclic GMP may potentiate lordosis behaviour by progesterone receptor activation.

Abstract

The purpose of this study was to test the hypothesis that cGMP acts as a progesterone substitute to facilitate lordosis in oestrogen-primed rats. Female Sprague-Dawley rats underwent stereotaxic surgery to place a 26-gauge guide cannula into the third ventricle. Bilateral ovariectomy was done at the same time as stereotaxic surgery. Five days later ovariectomized rats were primed with 2 microg estradiol benzoate 24 and 48 h prior to behaviour testing. Some animals were further injected with 200 microg progesterone 4 h before behaviour testing. A nitric oxide synthase inhibitor infused into the third ventricle before progesterone administration significantly reduced lordosis performance. 8-Bromo-cGMP, a cell permeable cGMP analogue, or saline vehicle was infused into the third ventricle of hormone-primed animals approximately 4 h prior to the first of 3-h behaviour tests. This cGMP analogue facilitated lordosis behaviour. We next used KT5823, a highly specific inhibitor of protein kinase G (PKG), to test the hypothesis that cGMP action is mediated by this kinase. In this experiment, KT5823 was infused 15 min before progesterone. KT5823 significantly decreased lordosis behaviour. RU486, a progesterone receptor antagonist, was used to assess whether the stimulatory effects of cGMP are mediated through the progesterone receptor. Oestrogen-primed animals were injected with 5 mg of RU486 or vehicle 60 min before infusion with 8-bromo-cGMP. RU486 significantly attenuated cGMP-facilitated lordosis behaviour. These data show that cGMP facilitates lordosis through activation of PKG and the progesterone receptor.

• Authors: H P Chu, J C Morales, A M Etgen
• Journal: Journal of neuroendocrinology (J Neuroendocrinol) Vol. 11 Issue 2 Pg. 107-13 (Feb 1999) ISSN: 0953-8194 [Print] United States
• PMID: 10048465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Alkaloids
• Carbazoles
• Enzyme Inhibitors
• Estrogens
• Hormone Antagonists
• Indoles
• Receptors, Progesterone
• KT 5823
• 8-bromocyclic GMP
• Mifepristone
• Progesterone
• Nitric Oxide Synthase
• Cyclic GMP
• NG-Nitroarginine Methyl Ester

Topics

• Alkaloids (pharmacology)
• Animals
• Brain (drug effects, enzymology)
• Carbazoles
• Cyclic GMP (analogs & derivatives, metabolism, pharmacology)
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Estrogens (pharmacology)
• Female
• Hormone Antagonists (pharmacology)
• Indoles
• Mifepristone (pharmacology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Posture (physiology)
• Progesterone (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Progesterone (metabolism)
• Sexual Behavior, Animal (drug effects, physiology)