sapogenins and estradiol-3-benzoate

Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance.

Topics: Adenosine Triphosphatases; Animals; Antigens, CD; Apyrase; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Fulvestrant; Ginsenosides; Hippocampus; Male; Nitriles; Pyrophosphatases; Rats; Sapogenins; Synaptosomes

Estrogen has well known effects on sexual behavior, however the role of the estrogen receptors (ER) alpha and beta on sexual behavior remains to be fully determined. This study investigated the individual and co-operative involvement of ERalpha and beta on sexual behaviors in the adult female rat. Subtype selective ER agonists, propyl-pyrazole triol (PPT; ERalpha agonist) and diarylpropionitrile (DPN; ERbeta agonist) were utilized to examine each receptor subtype's contribution, individual and co-operative, for both receptive (lordosis) and proceptive (hopping/darting, 'ear wiggling') female sexual behaviors. Ovariectomized female rats received subcutaneous injections of either: sesame oil (OIL), dimethylsulfoxide (DMSO), estradiol benzoate (EB; 10 microg/0.1 ml OIL), one of three doses of the ERalpha agonist PPT (1.25mg, 2.5mg or 5.0mg/0.1 ml DMSO), one of three doses of the ERbeta agonist DPN (1.25mg, 2.5mg or 5.0mg/0.1 ml DMSO) or a combination dose of PPT and DPN (2.5mg PPT+2.5mg DPN/0.1 ml DMSO) for two consecutive days, 48 and 24h prior to testing followed by a progesterone injection (500 microg/0.1 ml OIL) 4h prior to testing in order to elicit sexual behavior. The ERalpha agonist PPT, but not the ERbeta agonist DPN, elicited both proceptive and receptive behavior. PPT at doses of 2.5 and 5.0mg significantly elicited lordosis and proceptive behavior ('ear wiggling', hopping and darting). Intriguingly, the administration of both agonists together at the 2.5mg dose resulted in reduced levels of proceptivity and receptivity, suggesting that ERbeta modulates ERalpha's ability to elicit receptive and proceptive sexual behavior.

Topics: Analysis of Variance; Animals; Behavior, Animal; Contraceptive Agents; Dose-Response Relationship, Drug; Drug Combinations; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Ginsenosides; NAD; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Sapogenins; Sexual Behavior, Animal