Transmitter Content and Afferent Connections of Estrogen-Sensitive Progestin Receptor-Containing Neurons in the Primate Hypothalamus

Abstract

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotrans-mitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypotha-lamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.

Progesterone Can Block Transmission of the Estradiol-Induced Signal for Luteinizing Hormone Surge Generation during a Specific Period of Time Immediately after Activation of the Gonadotropin-Releasing Hormone Surge-Generating System

“…An indirect action of progesterone on GnRH secretion is supported by the findings of immunohistochemical studies, which have shown that, though progesterone receptors exist in a variety of different neuronal phenotypes, classical progesterone receptors, in the majority of species, are not found within GnRH cell bodies (27,28). Which (if any) of these progesterone-receptive neurons are involved in the inhibitory effects of progesterone on the generation of the GnRH surge and whether they lie within, or impinge upon, the estradiol signal transmission pathway, however, remains to be elucidated.…”

Estrogen Induces Ultrastructural Changes in Progesterone Receptor-Containing GABA Neurons of the Primate Hypothalamus

“…Our previous colocalization studies in primates failed to demonstrate PR-containing GNRH-producing cells [23]. However, it has been reported that a small population (< 10%) of LHRH-immunoreactive neurons in the guinea pig preoptic area exhibit nuclear immunoreactivity for PR [14], As it was mentioned in the introduction, progesterone 115, 16] as well as GABA [5,18] administration result in a decrease of GNRH neuronal activity.…”

Progesterone-Receptive β-Endorphin and Dynorphin B Neurons in the Arcuate Nucleus Project to Regions of High Gonadotropin-Releasing Hormone Neuron Density in the Ovine Preoptic Area

“…Thus, this species is an ideal model to study the neuronal systems targeted by progesterone to inhibit the neuroendocrine reproductive axis. The effects of progesterone on GnRH are indirect as GnRH neurons in the ewe [5] and other species [6,7,8] do not contain progesterone receptors (PR). This suggests that interneuronal systems relay the inhibitory signal.…”