Localization of the synthetic progestin 3H-ORG 2058 in neurons of the primate brain: evidence for the site of action of progestins on behavior

Abstract

The location of neurons that concentrate progestin in the brains of female cynomolgus monkeys was mapped by autoradiography using the specific synthetic progestin receptor ligand 3H-ORG 2058. Three females were ovariectomized and treated with estrogen (20 micrograms estradiol benzoate daily for 7 days), and one of them was also pretreated with progesterone. Each received an i.v. injection of 1 mCi 3H-ORG 2058 and was killed 1 hour later. Thaw-mount autoradiograms revealed intense accumulation of radioactivity in the nuclei of many neurons in the mediobasal hypothalamus, particularly in the ventromedial nucleus (n.), arcuate n., and premammillary n. Neuronal labeling was also observed frequently in the medial preoptic n., and occasionally in the anterior hypothalamic area, paraventricular n., and organum vasculosum of the lamina terminalis. In the pituitary gland, about 5% of cells in the pars distalis were intensely labeled. In the female pretreated with progesterone, however, labeling was almost completely blocked. Analysis of samples by high-performance liquid chromatography demonstrated that the radioactivity extracted from brain and pituitary gland cell nuclei was almost entirely unmetabolized 3H-ORG 2058. The nuclear concentration of progestin was much greater in the pituitary gland than in the brain, and was greater in the hypothalamus than in any other brain area. These results revealed well-localized groups of progestin-concentrating neurons in the primate brain which presumably mediate the effects of progesterone on both gonadotropin secretion and female sexual behavior.