Dilute Estradiol Implants and Progestin Receptor Induction in the Ventromedial Nucleus of the Hypothalamus: Correlation with Receptive Behavior in Female Rats*

Abstract

The ventromedial nucleus of the hypothalamus (VMN) is thought to constitute an essential neural substrate for hormonal induction of female sexual behavior. In previous work, implants of dilute (0.4%) estradiol (E2) have been found to prime progesterone-facilitated female sexual behavior in rats only when they are within or very close to the VMN. In other studies, induction of cytosolic progestin receptors (PRc) in the hypothalamus has been correlated with systemic E2 priming of receptive behavior. We combined dilute E2 implants with a Palkovits punch microassay for PRc in the an effort to examine the relationship between estrous behavior and estrogen-induced PRc in the VMN of individual female rats. Ovariectomized rats were given bilateral guide cannulae aimed at the VMN and were primed for 3 days with 1) blank implants plus oil sc, 2) blank implants plus 0.5 micrograms E2 benzoate sc, 3) implants of 0.4% E2 in cholesterol, or 4) implants of 2.0% E2. On day 4 all rats received progesterone (P) sc and were tested for receptive behavior. The following week all subjects received the same estrogen-priming treatment but were killed on day 4 without P treatment. The VMN was punch dissected and assayed for PRc. High levels of lordosis were seen in the E2 benzoate-treated and 2.0% E2-implanted animals, while little behavior was seen in the oil-treated animals. Among 0.4% E2-implanted animals, higher levels of lordosis were observed in subjects with implant placements in the rostral than in the caudal VMN; however, lordosis quotients were not correlated with PRc induction measured in the entire VMN of individual animals. In general, our findings suggest that local estrogenic stimulation of target cells in the VMN is capable of both priming the estrous response and induction of P receptors. Whether these two effects are causally related awaits future study.

Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

“…Effectiveness of ERa AS-ODN administration to knock down ERa is revealed by reduced ERa immunoreactive cells in the brain in ovx, E 2 -primed rats administered ERa AS-ODNs compared to rats administered control infusions or ERbAS-ODNs demonstrating that ERa-ODNs were effective in knocking down ERa. Indeed, E 2 administration to the VMH increases lordosis of ovx female rodents (Pleim et al, 1989). Given that 17b-E 2 has equal affinity for ERa and ERb, an interesting question is whether the observed effects for 17b-E 2 when administered to the hippocampus or VMH are also observed with ERa or ERb specific SERMS.…”

“…Immunohistochemical analyses of brain regions that are known to be involved in E 2 's effects on anxiety and reproduction, the hippocampus and VMH (Pleim et al, 1989), were performed. Brains were cut on coronal sections at 50 mm using a Vibratome.…”

“…The mating posture of female rodents, lordosis, depends upon initiation by E 2 in the VMH (Pfaff, 1980(Pfaff, , 1999(Pfaff, , 2005. Administration of E 2 to the VMH promotes lordosis and E 2 's effects can be obviated by subcutaneous administration of ER antagonists or blockade of ER binding in the VMH (Etgen and Shamamian, 1986;Etgen, 1987;Pleim et al, 1989). ER expression in the VMH is primarily ERa (Shughrue et al, 1997.…”

Estrogen Selectively Regulates Spine Density within the Dendritic Arbor of Rat Ventromedial Hypothalamic Neurons

“…Female rat sexual behavior has become a valuable model system, in part because the macrocircuitry and hormonal influences are well described (Pfaff et al, 1994). The actions of estrogen in the ventromedial nucleus of the hypothalamus (VMH) are crucial to the promotion of this behavior, as demonstrated by lesion, local infusion, and electrical stimulation experiments (Mathews and Edwards, 1977a,b;Pfaff and Sakuma, 1979a,b;Davis et al, 1982;Pleim et al, 1989). Additionally, receptor autoradiography, immunocytochemistry, and in situ hybridization have demonstrated the presence of estrogen receptors in the VMH (Pfaff and Keiner, 1973;Simerly et al, 1990;DonCarlos et al, 1991).…”

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

“…P 4' s actions in the VMH for lordosis P 4 's effects in the VMH to initiate lordosis can occur via traditional actions at intracellular progestin receptors (PRs) and induction of gene transcription. Classic intracellular PRs are highly expressed in the VMH of rodents and are upregulated by E 2 and/or P 4 coincident with lordosis [8][9][10]. Blocking actions at PRs in the VMH inhibits lordosis of naturally-receptive or ovx, hormone-primed rats [11][12][13][14][15][16].…”