It is all About the Chase: Neurosteroidogenesis in Male Rats is Driven by Control of Mating Pace.

Background: Masculine sexual behaviors are dependent on androstane-derived steroids; however, the modulatory effects of mating, and of mating control, on androstane neurosteroidogenesis remain largely unknown.

Objective: Herein, we investigated the effects of mating control, prior sexual experience, and age on brain region specific neurosteroidogenic responses in male rats.

Methods: Effects of acute sexual experience were tested in naïve male rats that either remained sexually- naïve, were exposed to a standard mating chamber, or were either given control of the mating pace in a standard mating chamber (male control) or mated wherein the female stimulus rat controlled the mating pace in a paced-mating chamber (female control).

Pregnant women with more seizures have lower allopregnanolone concentrations.

Neuroactive steroids have rapid, nongenomic effects on neuronal excitability. The effects in humans are less clear. We compared seizure control and concentrations of neuroactive steroids, known to influence neuroexcitability in animal studies, in pregnant women.

Progesterone's Effects on Cognitive Performance of Male Mice Are Independent of Progestin Receptors but Relate to Increases in GABA Activity in the Hippocampus and Cortex.

Progestogens' (e.g., progesterone and its neuroactive metabolite, allopregnanolone), cognitive effects and mechanisms among males are not well-understood.

Mating Enhances Expression of Hormonal and Trophic Factors in the Midbrain of Female Rats.

Among female rats, mating enhances neurosteroid formation in the midbrain ventral tegmental area (VTA; independent of peripheral steroid-secreting glands, ovaries, and adrenals). The sources/targets for these actions are not well understood. In Experiment 1, proestrous rats engaged in a mating paradigm, or did not, and the midbrains had been assessed the Affymetrix rat genome microarrays.

Learning and the Lifespan: What's Sex Got to Do With It?

Engagement in sexual behavior can impact neurosteroidogenesis, in particular production of the prohormone testosterone (T) and likely its subsequent metabolism to 5α-androstane-3α-17β-Diol (3α-Diol) or aromatization to estradiol (E). Androgens and their metabolites vary across the lifespan and impact many behaviors, including cognition, anxiety, and sexual behavior. Thus, we hypothesized that mating may alter cognitive performance via androstane neurosteroids in an age- and experience-dependent manner.

Prenatal resident-intruder stress decreases levels of allopregnanolone in the cortex, hypothalamus, and midbrain of males, and increases levels in the hippocampus and cerebellum of female, juvenile rat offspring.

Prenatal stress (PNS) can influence behaviors associated with cognition, reward and emotional regulation, which are controlled by brain areas such as the cortex, hippocampus, hypothalamus, midbrain and cerebellum. Allopregnanolone in these regions modulates behavioral and parasympathetic effects. The current study tested whether exposing pregnant dams to 5 days of resident-intruder stress on prenatal days 15-20 for 10 min altered the levels of allopregnanolone in cortex, hypothalamus, hippocampus, midbrain, and cerebellum of male and female juvenile offspring.

Central Actions of 3α,5α-THP Involving NMDA and GABA Receptors Regulate Affective and Sexual Behavior of Female Rats.

The neurosteroid, 5α-pregnan-3α-ol-20-one (known as "allopregnanolone" or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate (NMDA) and GABA receptors to facilitate rodent sexual behavior. Progestogens can also have anti-anxiety effects, but whether these involve actions of centrally-derived 3α,5α-THP or these receptors to support reproductively-relevant behavior is not well understood. We investigated the extent to which 3α,5α-THP's actions NMDA and/or GABA receptors in the midbrain VTA influence reproductive behaviors.

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli.

Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports.

Research Brief: Self-Reports of a Constellation of Persistent Antiandrogenic, Estrogenic, Physical, and Psychological Effects of Finasteride Usage Among Men.

Our research objective is to understand more, through subjective, self-reports on discussion boards/forums, persons' experiences associated with the use of drugs that alter androgen metabolism, such as finasteride. Finasteride is an orally active, specific inhibitor of 5α-reductase, which is localized to many androgen-dependent tissues. Finasteride inhibits the conversion of testosterone (T) to dihydrotestosterone (DHT), and is commonly used to treat benign prostatic hypertrophy (BPH) and male pattern baldness (MPB), both disorders associated with elevated DHT levels and 5α-reductase activity in the prostate and hair follicles, respectively.

Effects of non-contingent cocaine on 3 alpha-androstanediol. II. Disruption of lordosis of proestrous rats.

Drug use influences sexual behavior, performance, and can be associated with increased sexual risk-taking. Our prior results using an animal model indicate that progestogens contribute to hormonally-mediated changes in sexual behavior of female rodents during acute cocaine exposure. Androgens, such as testosterone, and its metabolite 3ɑ-androstanediol (3α-diol), and estradiol, are known to influence male sexual behavior, but can also alter the expression of sexual behavior of female rodents.

Effects of non-contingent cocaine on 3alpha-androstanediol. I. Disruption of male sexual behavior.

One of the hallmarks of drug abuse is a reduction in the salience of, and motivation for, natural rewards, such as mating. The effects of psychostimulants on male sexual interest and performance are conflicting; use of psychostimulants can produce increases in risky sexual behaviors but have detrimental effects on sexual ability. We hypothesize that these conflicting effects on sexual behavior are due to interactions between cocaine and androgens, such as testosterone and its neuroactive metabolite, 3α-androstanediol (3α-diol).

Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice.

There is currently a lack of understanding how genetic background and sex differences attribute to the heterogeneity of obsessive-compulsive disorder (OCD). An animal model of compulsive-like behaviors has been developed through bidirectional selection of house mice (Mus musculus) for high (big cotton nests; BIG mice) and low levels (small nests; SMALL mice) of nest-building behavior. The BIG male strains have predictive and face validity as a spontaneous animal model of OCD.

Endocrine disrupting chemicals and ovulation: Is there a relationship?

Although the potential for endocrine disrupting chemicals (EDCs) to disrupt female fecundity is great, few studies have assessed the threat to human reproduction. This study investigates levels of organochlorines in relation to their impact on women's menstrual cycles and ovulatory status. To address concerns of the Akwesasne Mohawk community in upstate New York regarding well-established exposure to EDCs, women's fertility and reproductive health endpoints, we recruited 215 women between the ages of 21 and 38 years to measure menstrual cycle characteristics and levels of local pollutants.

Progestogens' effects and mechanisms for object recognition memory across the lifespan.

This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory. Progesterone and its metabolites, in particular allopregnanolone, exert various effects on both cognitive and non-mnemonic functions in females. The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan, which will be discussed herein.

Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men.

Purpose: Our primary objective was to assess associations between urine cortisol as a biomarker of psychological stress and in vitro fertilization (IVF) outcomes. A secondary objective was to assess associations between toxic metals and cortisol.

Methods: Urine and blood specimens were collected from 52 women and 28 male partners completing a first IVF procedure, on the day of oocyte retrieval.

Neurochemical and behavioral effects of chronic unpredictable stress.

Chronic stress can influence behaviors associated with medial prefrontal cortex (mPFC) function, such as cognition and emotion regulation. Dopamine in the mPFC is responsive to stress and modulates its behavioral effects. The current study tested whether exposure to 10 days of chronic unpredictable stress (CUS) altered the effects of acute elevation stress on dopamine release in the mPFC and on spatial recognition memory.

Allopregnanolone levels and seizure frequency in progesterone-treated women with epilepsy.

Objective: To determine whether allopregnanolone (AP) may mediate seizure reduction in progesterone-treated women with epilepsy.

Methods: The NIH Progesterone Trial compared the efficacy of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects, randomized 2:1 to progesterone or placebo, stratified by catamenial vs noncatamenial designation. Treatments were compared on proportions of 50% responders, and changes in seizure frequency from 3 baseline to 3 treatment cycles.

The pregnane xenobiotic receptor, a prominent liver factor, has actions in the midbrain for neurosteroid synthesis and behavioral/neural plasticity of female rats.

A novel factor of interest for growth/plasticity in the brain is pregnane xenobiotic receptor (PXR). PXR is a liver factor known for its role in xenobiotic clearance and cholesterol metabolism. It is expressed in the brain, suggesting a potential role for plasticity, particularly involving cholesterol-based steroids and neurosteroids.

Novel receptor targets for production and action of allopregnanolone in the central nervous system: a focus on pregnane xenobiotic receptor.

Neurosteroids are cholesterol-based hormones that can be produced in the brain, independent of secretion from peripheral endocrine glands, such as the gonads and adrenals. A focus in our laboratory for over 25 years has been how production of the pregnane neurosteroid, allopregnanolone, is regulated and the novel (i.e.

Female mice with deletion of Type One 5α-reductase have reduced reproductive responding during proestrus and after hormone-priming.

The capacity to form progesterone (P₄)'s 5α-reduced metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP; a.k.a.

Endocrine-disrupting chemicals: elucidating our understanding of their role in sex and gender-relevant end points.

Endocrine-disrupting chemicals (EDCs) are diverse and pervasive and may have significant consequence for health, including reproductive development and expression of sex-/gender-sensitive parameters. This review chapter discusses what is known about common EDCs and their effects on reproductively relevant end points. It is proposed that one way that EDCs may exert such effects is by altering steroid levels (androgens or 17-estradiol, E₂) and/or intracellular E₂ receptors (ERs) in the hypothalamus and/or hippocampus.

Brain levels of prostaglandins, endocannabinoids, and related lipids are affected by mating strategies.

Background. Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. Likewise, prostaglandins (PGs) drive sexual differentiation and initiation of ovulation.

Progesterone-facilitated lordosis of estradiol-primed mice is attenuated by knocking down expression of membrane progestin receptors in the midbrain.

Evidence is emerging of the role of membrane progestin receptors (referred to as mPRs herein: members of Progestin and AdipoQ Receptor (Paqr) family) as a novel brain target in mammals, such as rats. In the present study, the role of mPRs in mice was assessed to further elucidate the conservation of this mechanism across species. The brain target investigated was the midbrain ventral tegmental area (VTA) given its described role for rapid actions of progestins for reproduction.

Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase Type 1 mutant, mice.

Progesterone (P4) facilitates exploration, anxiety and social behaviors in estrogen (E2)-primed mice. Some of these effects may be due to actions of its 5α-reduced metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP). In order to address the role of P4 and its metabolite, 3α,5α-THP, a mouse model was utilized.

Progesterone, compared to medroxyprogesterone acetate, to C57BL/6, but not 5α-reductase mutant, mice enhances object recognition and placement memory and is associated with higher BDNF levels in the hippocampus and cortex.

Progesterone (P4) may influence cognition in part through actions of its 5α-reduced metabolite, allopregnanolone. Ovariectomized mice that were C57BL/6 wildtype (WT), or deficient in the 5α-reductase Type 1 enzyme (5α-reductase knockout; 5αRKO), were administered vehicle, P4, allopregnanolone, or medroxyprogesterone acetate (MPA) after training in the object recognition or placement tasks. WT mice administered P4 or allopregnanolone performed significantly better in the object recognition and placement tasks than did WT mice administered vehicle or MPA.