estradiol-3-benzoate and Lordosis

Intracerebroventricular (ICV) administration of estradiol benzoate (E

Topics: Animals; Estradiol; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Lordosis; Ovariectomy; Progesterone; Rats; Sexual Behavior, Animal

Clinical studies have shown altered sexual function in people with diabetes; basic science studies, using the streptozotocin (STZ)-induced animal model of type 1 diabetes mellitus (DM1), have consistently reported decreased sexual behavior in hyperglycemic female animals, but features of sexual motivation and aggressive behavior have not been explored in these animals.. To study several parameters that denote sexual motivation in STZ-treated female rats and to compare behavioral features of sexual behavior and aggression in non-paced mating (NPM) and paced mating (PM) conditions.. DM1 was induced by injecting STZ (diluted in citrate buffer) at a dose of 50 mg/kg intraperitoneally over 2 consecutive days into ovariectomized Wistar rats. 10 days later, female rats were treated with estradiol benzoate (10 μg, -24 hours) and progesterone (3 mg, -4 hours); their sexual behavior (including lordosis quotient, lordosis intensity, and proceptivity) and aggression were evaluated under NPM and PM conditions. Body weight, blood glucose levels, and spontaneous ambulatory activity also were measured. A group of STZ-treated animals was administered a long-acting insulin analogue (glargine) every 12 hours for 8 days, and their sexual and aggressive behaviors were evaluated in NPM.. We quantified body weight, blood glucose level, spontaneous ambulatory activity, and sexual and aggressive behaviors in NPM and PM; the time the female rats spent interacting with the male rat or in the male rat's chamber also was registered in PM.. Compared with controls, STZ-treated ovariectomized rats lost body weight, had increased blood glucose levels, and had unchanged spontaneous ambulatory activity. In the PM and NPM conditions, animals showed decreased lordosis quotient and lordosis intensity, increased aggression, and unaltered proceptivity, although in NPM the effects of STZ treatment on aggression were more drastic and were completely prevented by insulin. In PM no differences were found between diabetic and control female rats in the time interacting with the male rat or in the male rat's chamber.. These findings support the observation of increased prevalence of sexual dysfunctions and aggression in the clinical setting of DM1.. The main strength of this study is that it analyzed sexual behavior under PM and NPM conditions and aggression in STZ-treated female rats. Its main limitations are that the model of DM1 represents only 10% of the affected population and that no specific treatment is proposed for the sexual dysfunctions.. These results suggest that STZ-treated rats have decreased sexual receptivity in NPM and PM, accompanied by increased aggressiveness in NPM. Hernández-Munive AK, Rebolledo-Solleiro D, Ventura-Aquino E, Fernández-Guasti A. Reduced Lordosis and Enhanced Aggression in Paced and Non-Paced Mating in Diabetic Female Rats. J Sex Med 2018;15:124-135.

Topics: Aggression; Animals; Diabetes Mellitus, Experimental; Estradiol; Female; Lordosis; Male; Motivation; Progesterone; Rats; Rats, Wistar; Sexual Behavior; Sexual Behavior, Animal; Streptozocin

Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERβ, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERβ, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERβ and/or the ERα-ERβ interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERβ, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERβ activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERβ increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERβ have different effects on the levels and subcellular location of PRs in VMNvl neurons.

Topics: Animals; Body Weight; Cell Nucleus; Cytoplasm; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation; Hypothalamus; Immunohistochemistry; Lordosis; Microscopy, Confocal; Neurons; Rats; Rats, Wistar; Receptors, Progesterone; Uterus

Sexual receptivity in the female rat is dependent on dose and duration of estradiol exposure. A 2 μg dose of estradiol benzoate (EB) primes reproductive behavior circuits without facilitating lordosis. However, 50 μg EB facilitates lordosis after 48 hours. Both EB doses activate membrane estrogen receptor-α (mERα) that complexes with and signals through metabotropic glutamate receptor-1a (mGluR1a). This mERα-mGluR1a signaling activates a multisynaptic lordosis-inhibiting circuit in the arcuate nucleus (ARH) that releases β-endorphin in the medial preoptic nucleus (MPN), activating μ-opioid receptors (MOP). MPN MOP activation is maintained, inhibiting lordosis for 48 hours by 2 μg EB, whereas 50 μg EB at 48 hours deactivates MPN MOP, facilitating lordosis. We hypothesized that 50 μg EB down-regulates ERα and mERα-mGluR1a complexes in the ARH to remove mERα-mGluR1a signaling. In experiment I, 48 hours after 2 μg or 50 μg EB, the number of ARH ERα-immunopositive cells was reduced compared with controls. In experiment II, compared with oil controls, total ARH ERα protein was decreased 48 hours after 50 μg EB, but the 2 μg dose was not. These results indicate that both EB doses reduced the total number of cells expressing ERα, but 2 μg EB may have maintained or increased ERα expressed per cell, whereas 50 μg EB appeared to reduce total ERα per cell. In experiment III, coimmunoprecipitation and Western blot revealed that total mERα and coimmunoprecipitated mERα with mGluR1a were greater 48 hours after 2 μg EB treatment vs rats receiving 50 μg EB. These results indicate 2 μg EB maintains but 50 μg EB down-regulates mERα-mGluR1a to regulate the lordosis circuit activity.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Cell Membrane; Dose-Response Relationship, Drug; Down-Regulation; Estradiol; Estrogen Receptor alpha; Estrogens; Female; Lordosis; Nerve Tissue Proteins; Neurons; Ovariectomy; Protein Multimerization; Protein Transport; Rats; Rats, Long-Evans; Receptors, Metabotropic Glutamate; Signal Transduction; Up-Regulation