Revisiting the neural role of estrogen receptor beta in male sexual behavior by conditional mutagenesis

Estradiol derived from neural aromatization of gonadal testosterone plays a key role in the perinatal organization of the neural circuitry underlying male sexual behavior. The aim of this study was to investigate the contribution of neural estrogen receptor (ER) β in estradiol-induced effects without interfering with its peripheral functions. For this purpose, male mice lacking ERβ in the nervous system were generated. Analyses of males in two consecutive tests with a time interval of two weeks showed an effect of experience, but not of genotype, on the latencies to the first mount, intromission, pelvic thrusting and ejaculation. Similarly, there was an effect of experience, but not of genotype, on the number of thrusts and mating length. Neural ERβ deletion had no effect on the ability of males to adopt a lordosis posture in response to male mounts, after castration and priming with estradiol and progesterone. Indeed, only low percentages of both genotypes exhibited a low lordosis quotient. It also did not affect their olfactory preference. Quantification of tyrosine hydroxylase- and kisspeptin-immunoreactive neurons in the preoptic area showed unaffected sexual dimorphism of both populations in mutants. By contrast, the number of androgen receptor- and ERα-immunoreactive cells was significantly increased in the bed nucleus of stria terminalis of mutant males.These data show that neural ERβ does not play a crucial role in the organization and activation of the neural circuitry underlying male sexual behavior. These discrepancies with the phenotype of global ERβ knockout models are discussed.     

Oxytocin in the medial preoptic area facilitates male sexual behavior in the rat

Oxytocin (OT) is a versatile neuropeptide that is involved in a variety of mammalian behaviors, and its role in reproductive function and behavior has been well established. The majority of pharmacological studies of the effects of OT on male sexual behavior have focused on the paraventricular nucleus (PVN), ventral tegmental area (VTA), hippocampus, and amygdala. Less attention has been given to the medial preoptic area (MPOA), a major integrative site for male sexual behavior. The present study investigated the effects of intra-MPOA administration of OT and (d(CH2)51, Tyr(Me)2, Thr4, Orn8, Tyr-NH29)-vasotocin, an OT antagonist (OTA), on copulation in the male rat. The relationship between OT receptor (OTR) binding levels in the MPOA and sexual efficiency was also explored. Microinjection of OT into the MPOA facilitated copulation in sexually experienced male rats, whereas similar injections of an OTA inhibited certain aspects of copulation but had no significant effect on locomotor activity in an open field. Contrary to expectation, sexually efficient males had lower levels of OTR binding in the rostral MPOA compared to inefficient animals. The present data suggest that OT activity in the MPOA is not necessary for the expression of male sexual behavior but is sufficient to facilitate copulatory behaviors and improve sexual efficiency in sexually experienced male rats. These data also suggest that OTR activity in the MPOA stimulates anogenital investigation, facilitates the initiation of copulation, and plays a role in the sensitization effect of the first ejaculation on subsequent ejaculations.     

雌激素受体α和β免疫反应在雄性和雌性棕色田鼠脑区分布的比较

单配制和多配制动物社会行为有差异,这些差异可能与雌激素受体类型有关（ERs）。虽然多配制大鼠和小鼠中枢神经雌激素受体α（ERα）和β（ERβ）免疫反应在大脑的分布已有报道,单配制雄性草原田鼠中枢神经ERα的分布也有报道,但单配制田鼠ERα和（或）ERβ在雌性和雄性分布差异未见报道。本研究对雄性和雌性棕色田鼠前脑区域ERα和ERβ免疫反应（IR）细胞数量进行比较。研究结果表明：（1）免疫反应主要分布在细胞核中。 （2）ERα-IR和ERβ-IR细胞广泛分布于整个雌性和雄性前脑区域,在许多脑区表达有重叠。然而,不同受体在雌雄不同脑核中的分布数量是不同的。（3）ERα 和ERβ的分布存在性别差异。例如,雌性ERα在视前核中部（MPN）,终纹床和（BNST）和杏仁内侧核（MeA）比雄性多,相反雄性ERβ在MPN和BNST比雌性多。这些研究结果可能为我们理解如何通过ERα和ERβ调节动物的社会行为,及雌性和雄性社会行为的差异提供一个重要的神经解剖学基础。     

Effect of forebrain implants of testosterone or estradiol on scent-marking and sexual behavior in male and female rabbits

Chinning consists of rubbing the chin against an object, thereby depositing secretions from the submandibular glands. As mating, chinning is stimulated in male and female rabbits by testosterone and estradiol, respectively. To investigate the brain sites where steroids act to stimulate chinning and mating we implanted into the ventromedial hypothalamus (VMH) or the medial preoptic area (MPOA) of gonadectomized male and female rabbits testosterone propionate (TP; males) or estradiol benzoate (EB; females) and quantified chinning and sexual behavior. EB implants into the VMH or MPOA reliably stimulated chinning in females. Most of those implanted into the VMH and around half of the ones receiving EB into MPOA or diagonal band of Broca (DBB) showed lordosis. Chinning, but not sexual behavior, was stimulated in males by TP implants into the MPOA or DBB. Neither chinning nor mounting were reliably displayed by males following TP implants into the VMH. Results indicate that, in females, the VMH is an estrogen-sensitive brain area that stimulates both chinning and lordosis while the MPOA seems to contain subpopulations of neurons involved in either behavior. In males, androgen-sensitive neurons of the MPOA, but not the VMH, are involved in chinning stimulation but it is unclear if these areas also participate in the regulation of copulatory behavior.     

Effect of forebrain implants of testosterone or estradiol on scent-marking and sexual behavior in male and female rabbits

Chinning consists of rubbing the chin against an object, thereby depositing secretions from the submandibular glands. As mating, chinning is stimulated in male and female rabbits by testosterone and estradiol, respectively. To investigate the brain sites where steroids act to stimulate chinning and mating we implanted into the ventromedial hypothalamus (VMH) or the medial preoptic area (MPOA) of gonadectomized male and female rabbits testosterone propionate (TP; males) or estradiol benzoate (EB; females) and quantified chinning and sexual behavior. EB implants into the VMH or MPOA reliably stimulated chinning in females. Most of those implanted into the VMH and around half of the ones receiving EB into MPOA or diagonal band of Broca (DBB) showed lordosis. Chinning, but not sexual behavior, was stimulated in males by TP implants into the MPOA or DBB. Neither chinning nor mounting were reliably displayed by males following TP implants into the VMH. Results indicate that, in females, the VMH is an estrogen-sensitive brain area that stimulates both chinning and lordosis while the MPOA seems to contain subpopulations of neurons involved in either behavior. In males, androgen-sensitive neurons of the MPOA, but not the VMH, are involved in chinning stimulation but it is unclear if these areas also participate in the regulation of copulatory behavior.     

Mating-induced expression of c-fos in the male Syrian hamster brain: Role of experience,pheromones, and ejaculations

This study was designed to investigate the effects of pheromonal cues and specific behaviors within the male copulatory sequence on c-fos expression in the medial nucleus of the amygdala (Me), the bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA) of the Syrian hamster brain. Sexually experienced male hamsters were placed into clean testing arenas and were either: 1) left alone as handled controls; 2) exposed to female hamster vaginal secretion (FHVS) on cotton swabs; or mated to various end points of copulation with a sexually receptive female: 3) five intromissions, 4) one ejaculation, 5) five ejaculations, or 6) long intromissions. A seventh group of sexually naive control males 7) was left alone in the arena. The brains of these males were compared to those of the sexually experienced controls to determine whether exposure to cues associated with prior sexual experience could alter c-fos expression. In males exposed only to FHVS, Fos immunoreactivity (Fos-ir) increased within the posterodorsal Me, the anterodorsal part of the posteromedial BNST, and the magnocellular medial preoptic nucleus (MPNmag). Following one ejaculation, Fos-ir increased within the caudal posterodorsal Me, the dorsolateral MPOA, and the paraventricular nucleus of the hypothalamus. After multiple ejaculations, additional labeling was observed within the posteroventral part of the posteromedial BNST, the medial preoptic nucleus (MPN), the central tegmental field, and in cell clusters of the caudal posterodorsal Me and rostral posteromedial BNST. Fos-ir also increased within the posterodorsal Me, MPN, and MPNmag in sexually experienced control males exposed to the empty test chamber compared to sexually naive males exposed to an identical chamber. These results demonstrate that the mating-induced pattern of neuronal activation in sexually experienced males is dependent upon multiple factors, including prior sexual experience in the testing environment, investigation of FHVS, and the number of ejaculations achieved. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 481–501, 1997     

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERα) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3 months) and middle-aged (12 months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERα immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERα cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERα cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERα expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men.     

Reversal of reproductive deficiency in the hpg male mouse by neonatal androgenization.

Some aspects of reproductive function in the GnRH-deficient hypogonadal (hpg) mutant mouse can be restored by transplanting normal fetal brain tissue containing GnRH cells into the central nervous system of adult hpg mice. However, hpg males showing physiological response to the graft fail to display sexual behavior and are infertile. We hypothesized that the reproductive deficit of these males is due to insufficient perinatal exposure to testicular androgens as a consequence of the GnRH deficiency. To test this hypothesis we androgenized hpg males by giving them neonatal injections of testosterone propionate (TP). Controls consisted of hpg males not androgenized neonatally and of normal males. All three groups received a TP implant in adulthood, and their copulatory behavior and reproductive capability were recorded. In addition, other hpg males, not androgenized neonatally, received fetal brain transplants containing GnRH neurons and were also tested for copulatory behavior and reproductive capability before and after receiving a TP implant. Three of 8 neonatally androgenized hpg males expressed the full repertoire of male sexual behavior, including intromission and ejaculation, and sired several litters. Three of 7 control hpg males that were not androgenized neonatally but received TP implants in adulthood also displayed mounting and intromission, but there was no evidence of ejaculation, and these males failed to impregnate normal females. Of the 8 hpg males that responded to a fetal transplant with testicular growth, only 1 displayed mounting behavior. However, when given a TP implant, 4 of 8 hpg males with grafts displayed mounting and intromissions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progesterone receptor in the forebrain of female gray short-tailed opossums: Effects of exposure to male stimuli

Progesterone receptor immunoreactivity (PRir) in brain areas involved in reproductive behavior in eutherian species was examined for the first time in a female marsupial, the gray short-tailed opossum (Monodelphis domestica, hereinafter, opossum). PRir in nuclei of neurons, measured as area covered by stained nuclei, was seen in the arcuate nucleus (Arc); anteroventral periventricular nucleus (AVPv); bed nucleus of the stria terminalis (BST); medial preoptic area (MPOA), and ventromedial hypothalamus (VMH), but not in control areas adjacent to the hypothalamus or cortex. Female opossums are induced into cytological, urogenital sinus (UGS), estrus by male pheromones and into behavioral estrus, i.e., receptivity, by pairing with a male, and both estradiol (E) and progesterone (P) are involved in induction of receptivity in intact and ovariectomized females. PRir in the AVPv, MPOA, and VMH was very low in females that had never been exposed to males or their scent marks, i.e., naïve anestrous (NVA) females, and either previous or current exposure to males or their scent marks was associated with elevated PRir. PRir was significantly higher in the AVPv and MPOA of anestrous females with previous but no current exposure to males and their scent marks, i.e., experienced anestrous (EXPA) females, than in NVA females, but PRir was significantly lower in the MPOA and VMH of EXPA females than in females that were behaviorally receptive and had recently copulated, i.e., behavioral receptive estrous (BRE) females. PRir was higher in the VMH of both UGS estrous (UGSE) and BRE females compared to that in EXPA animals, but PRir did not differ between UGSE and BRE females in any of the 3 brain areas examined, including the MPOA These results provide evidence that pheromonal induction of estrus and sexual receptivity in opossums is associated with elevation of PRir in the VMH and MPOA and that prior exposure to males or their pheromones, even in the absence of current male stimuli, is associated with persistent elevation of PRir in the AVPv and MPOA.     

Specific activation of estrogen receptor alpha and beta enhances male sexual behavior and neuroplasticity in male Japanese quail

Two subtypes of estrogen receptors (ER), ERα and ERβ, have been identified in humans and numerous vertebrates, including the Japanese quail. We investigated in this species the specific role(s) of each receptor in the activation of male sexual behavior and the underlying estrogen-dependent neural plasticity. Castrated male Japanese quail received empty (CX) or testosterone-filled (T) implants or were daily injected with the ER general agonist diethylstilbestrol (DES), the ERα-specific agonist PPT, the ERβ-specific agonist DPN or the vehicle, propylene glycol. Three days after receiving the first treatment, subjects were alternatively tested for appetitive (rhythmic cloacal sphincter movements, RCSM) and consummatory aspects (copulatory behavior) of male sexual behavior. 24 hours after the last behavioral testing, brains were collected and analyzed for aromatase expression and vasotocinergic innervation in the medial preoptic nucleus. The expression of RCSM was activated by T and to a lesser extent by DES and PPT but not by the ERβagonist DPN. In parallel, T fully restored the complete sequence of copulation, DES was partially active and the specific activation of ERα or ERβ only resulted in a very low frequency of mount attempts in few subjects. T increased the volume of the medial preoptic nucleus as measured by the dense cluster of aromatase-immunoreactive cells and the density of the vasotocinergic innervation within this nucleus. DES had only a weak action on vasotocinergic fibers and the two specific ER agonists did not affect these neural responses. Simultaneous activation of both receptors or treatments with higher doses may be required to fully activate sexual behavior and the associated neurochemical events.     

Male sexual behavior in deer mice (Peromyscus maniculatus) following castration and hormone replacement

Sexually experienced male deer mice (Peromyscus maniculatus bairdi) were castrated and tested for male sexual behavior. In the weeks following castration male sexual behavior decreased. Ejaculation disappeared first, followed by intromission and, finally, mounting. Castrated males failing to copulate were assigned to one of four treatment groups: 200 μg testosterone propionate (TP); 200 μg dihydrotestosterone propionate (DHTP); 2 μg estradiol benzoate (EB); or sesame oil (OIL). TP and DHTP were equally effective in restoring the complete male sexual behavior pattern. In contrast, EB was effective in stimulating mounting and minimally effective in stimulating intromissions (vaginal penetration), but did not stimulate ejaculatory responses. These data indicate that in deer mice testosterone may mediate male sexual behavior through reduction to dihydrotestosterone rather than through aromatization to estradiol.     

Sexual experience changes sex hormones but not hypothalamic steroid hormone receptor expression in young and middle-aged male rats

Testosterone is well known to regulate sexual behavior in males, but this is dependent upon prior sexual experience. Aging is associated with decreased libido and changes in testosterone, but the role of experience in these age-related processes has not been systematically studied. We examined effects of age and sexual experience on serum hormones (total testosterone, free testosterone, estradiol, LH) and on numbers of androgen receptor (AR) and estrogen receptor α (ERα) immunoreactive cells in the hypothalamus. Extensive sexual experience was given to male rats at 4 months of age. Rats were euthanized at either 4 months (young) or 12 months (middle-aged (MA)). Comparable sexually naïve male rats were handled and placed into the testing arena but did not receive any sexual experience. Thus, we had four groups: young-naïve, young-experienced, MA-naïve and MA-experienced. Serum hormone levels were assayed, and numbers of AR and ERα cells were quantified stereologically in the medial preoptic nucleus (MPN) and the anteroventral periventricular nucleus (AVPV). Sexually experienced males had significantly elevated serum testosterone and free testosterone in both age groups. Both total and free testosterone were higher, and estradiol lower, in middle-aged than young rats. Experience did not alter either AR or ERα expression in the preoptic brain regions studied. Aging was associated with increased expression of AR, but no change in ERα. These results show that sexual experience can induce short-term and long-term alterations in serum hormones but these effects are not manifested upon their receptors in the hypothalamus.     

Olfactory preference in the male rat depends on multiple chemosensory inputs converging on the preoptic area

Both volatile and nonvolatile molecules are involved in chemosensory communication in rodents. Volatile odors from physically inaccessible estrous females induced increased numbers of c-Fos-positive cells in the preoptic area (POA) and in the cortical nucleus of the amygdala (CoA) of male rats. The numbers of c-Fos-positive cells in the medial nucleus of the amygdala (MeA) increased in response to the nonvolatile odors of bedding soiled with the excreta of estrous females. In an alternate choice paradigm, male rats carrying ibotenic acid lesions in either the MeA or the CoA—or a combination of both—distinguished the odors of estrous females from those of males, although the time spent sniffing the stimuli was diminished. Males with POA lesions showed complete loss of this capability. Males carrying either of the lesions did not detect differences between estrous and anestrous females or between intact and orchidectomized males. Lesions in the POA or MeA severely impaired male sexual behavior, whereas a CoA lesion had no effects. Thus, c-Fos-positive cells in the CoA might be involved in chemosensory transmission relevant to certain social contexts, but not in the execution of male sexual behavior. The POA is indispensable for both olfactory preferences and sexual behavior. The residual olfactory preference in males with MeA or CoA lesions or the combination of both could reflect an additional route for chemosensory transmission from the main olfactory bulb to the POA.     

Endogenous oxytocin is necessary for preferential Fos expression to male odors in the bed nucleus of the stria terminalis in female Syrian hamsters

Successful reproduction in mammals depends on proceptive or solicitational behaviors that enhance the probability of encountering potential mates. In female Syrian hamsters, one such behavior is vaginal scent marking. Recent evidence suggests that the neuropeptide oxytocin (OT) may be critical for regulating this behavior. Blockade of OT receptors in the bed nucleus of the stria terminalis (BNST) or the medial preoptic area (MPOA) decreases vaginal marking responses to male odors; lesion data suggest that BNST, rather than MPOA, mediates this effect. However, how OT interacts with sexual odor processing to drive preferential solicitation is not known. To address this issue, intact female Syrian hamsters were exposed to male or female odors and their brains processed for immunohistochemistry for Fos, a marker of recent neuronal activation, and OT. Additional females were injected intracerebroventricularly (ICV) with an oxytocin receptor antagonist (OTA) or vehicle, and then tested for vaginal marking and Fos responses to sexual odors. Colocalization of OT and Fos in the paraventricular nucleus of the hypothalamus was unchanged following exposure to male odors, but decreased following exposure to female odors. Following injections of OTA, Fos expression to male odors was decreased in BNST, but not in MPOA or the medial amygdala (MA). Fos expression in BNST may be functionally relevant for vaginal marking, given that there was a positive correlation between Fos expression and vaginal marking for BNST, but not MPOA or MA. Together, these data suggest that OT facilitation of neuronal activity in BNST underlies the facilitative effects of OT on solicitational responses to male odors.     

Sex differences in the inhibition by ATD of testosterone-activated mounting behavior in guinea pigs

Adult male and female guinea pigs from a genetically heterogeneous stock were gonadectomized and tested for mounting behavior before and during various treatments with testosterone cypionate (TC) alone or in combination with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). ATD was implanted subdermally in Silastic capsules (either 1 or 2 in females; 2 or 3 in males). In females 2 capsules of ATD completely blocked the behavioral effects of TC, and 1 capsule was an effective blocker in 58% of the females. The blocking effect was reversed by injection of diethylstilbestrol. In males, there was no measurable effect of ATD on mounting activity even when 3 capsules were implanted. Moreover, the TC induction of higher components of male sexual behavior (intromission and ejaculation) was also not impaired by ATD. Results are interpreted as indicating that either the process of male sexual differentiation or the male genotype eliminates the requirement for aromatization in androgenic activation of sexual behavior.     

Impaired male sexual behavior in activin receptor type II knockout mice

Integration of multiple hormonal and neuronal signaling pathways in the medial preoptic area (mPOA) is required for elicitation of male sexual behavior in most vertebrates. Perturbation of nitric oxide synthase (NOS) activity in the mPOA causes significant defects in male sexual behavior. Although activins and their signaling components are highly expressed throughout the brain, including the mPOA, their functional significance in the central nervous system (CNS) is unknown. Here, we demonstrate a neurophysiologic role for activin signaling in male reproductive behavior. Adult activin receptor type II null (Acvr2-/-) male mice display multiple reproductive behavioral deficits, including delayed initiation of copulation, reduced mount, and intromission frequencies, and increased mount, intromission, and ejaculation latencies. These behavioral defects in the adult mice are independent of gonadotropin-releasing hormone (GnRH) homeostasis or mating-induced changes in luteinizing hormone (LH) and testosterone levels. The impairment in behavior can be correlated to the nitric oxide content in the CNS because Acvr2-/- males have decreased NOS activity in the mPOA but not the rest of the hypothalamus or cortex. Olfactory acuity tests confirmed that Acvr2-/- mice have no defects in general odor or pheromone recognition. In addition, motor functions are not impaired and the mutants demonstrate normal neuromuscular coordination and balance. Furthermore, the penile histology in mutant mice appears normal, with no significant differences in the expression of penile differentiation marker genes compared with controls, suggesting the observed behavioral phenotypes are not due to structural defects in the penis. Our studies identify a previously unrecognized role of activin signaling in male sexual behavior and suggest that activins and/or related family members are upstream regulators of NOS activity within the mPOA of the forebrain.     

Nitric oxide synthase in mating behavior circuitry of male Syrian hamster brain

Chemosensory and hormonal stimuli are essential for mating in the male Syrian hamster. These signals are processed in a neural circuit that includes the medial amygdaloid nucleus (Me), bed nucleus of the stria terminalis (BNST), and medial preoptic area (MPOA). Nitric oxide is implicated in the regulation of male sexual behavior, and nitric oxide synthase (NOS), the enzyme that catalyzes the production of nitric oxide, is present in the limbic system. In this study, the distribution of NOS-containing neurons in mating behavior circuitry of the male Syrian hamster brain was determined using labeling for brain NOS (bNOS) and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). bNOS and NADPH-d labeled equivalent populations of neurons. NOS-containing neurons were clustered in specific subnuclei within the Me, BNST, and MPOA. NOS-positive fibers and neurons were seen in the stria terminalis and ventral amygdalofugal pathway, which link the Me with BNST and MPOA. Many NOS-positive neurons in the posterior subdivision of the Me, the medial preoptic nucleus (MPN), and the ventral premammillary nucleus contain androgen receptors. Castration reduced NOS-positive neurons in the MPN, implying a selective regulation of NOS by gonadal steroids. Together, these results suggest that NOS may contribute to the regulation of male sexual behavior by influencing the central neural processing of hormonal and chemosensory signals in the hamster limbic system. © 1996 John Wiley & Sons, Inc.     

Increased Dendritic Spine Density and Tau Expression Are Associated with Individual Differences in Steroidal Regulation of Male Sexual Behavior

Male sexual behavior (MSB) is modulated by gonadal steroids, yet this relationship is highly variable across species and between individuals. A significant percentage (∼30%) of B6D2F1 hybrid male mice demonstrate MSB after long-term orchidectomy (herein after referred to as “maters”), providing an opportunity to examine the mechanisms that underlie individual differences in steroidal regulation of MSB. Use of gene expression arrays comparing maters and non-maters has provided a first pass look at the genetic underpinnings of steroid-independent MSB. Surprisingly, of the ∼500 genes in the medial preoptic area (MPOA) that differed between maters and non-maters, no steroid hormone or receptor genes were differentially expressed between the two groups. Interestingly, best known for their association with Alzheimer’s disease, amyloid precursor protein (APP) and the microtubule-associated protein tau (MAPT) were elevated in maters. Increased levels of their protein products (APP and tau) in their non-pathological states have been implicated in cell survival, neuroprotection, and supporting synaptic integrity. Here we tested transgenic mice that overexpress tau and found facilitated mounting and intromission behavior after long-term orchidectomy relative to littermate controls. In addition, levels of synaptophysin and spinophilin, proteins generally enriched in synapses and dendritic spines respectively, were elevated in the MPOA of maters. Dendritic morphology was also assessed in Golgi-impregnated brains of orchidectomized B6D2F1 males, and hybrid maters exhibited greater dendritic spine density in MPOA neurons. In sum, we show for the first time that retention of MSB in the absence of steroids is correlated with morphological differences in neurons.     

Differential effects of bromocriptine treatment on LH release and copulatory behavior in hyperprolactinemic male rats

Hyperprolactinemia (hyperPRL) induced by grafting four pituitary glands under the kidney capsule suppresses copulatory behavior in male rats and sexually naive male mice. In mice sexual experience attenuates the suppressive effects of hyperPRL on mating behavior, thus a comparison of the behavioral consequences of inducing hyperPRL in sexually naive and experienced male rats was undertaken. Hyperprolactinemia had a significant suppressive effect on mating behavior in both groups of animals. Experienced animals showed deficits in all parameters studied except mount frequency and postejaculatory interval, while naive animals differed from respective controls only in mount latency, intromission latency, and intromission frequency. To determine if the inhibition of chronically elevated prolactin (PRL) levels would reverse the suppression of gonadotropin secretion and copulatory behavior in hyperprolactinemic animals, the effects of bromocriptine (CB-154) administration on plasma hormone levels and mating behavior were examined in pituitary-grafted and control rats. Bromocriptine treatment (1 mg/day for 14 days) led to increases in sexual activity in both the sham-operated and grafted animals. In the grafted animals, plasma PRL was reduced and plasma LH significantly increased in the CB-154-treated animals when compared to oil-treated controls. In sham-operated animals, CB-154 produced no significant changes in plasma LH or FSH despite the suppressed PRL levels. These results indicate that (1) hyperPRL induced by pituitary grafts can cause deficits in mating behavior in male rats despite previous sexual experience, and (2) while CB-154 may be acting through other mechanisms to stimulate copulatory behavior, the reduction of chronically elevated PRL levels due to CB-154 treatment is responsible for reversal of the suppressive effects of hyperPRL on LH secretion.     

Sexually dimorphic androgen and estrogen receptor mRNA expression in the brain of túngara frogs

Sex steroid hormones are potent regulators of behavior and they exert their effects through influences on sensory, motor, and motivational systems. To elucidate where androgens and estrogens can act to regulate sex-typical behaviors in the túngara frog (Physalaemus pustulosus), we quantified expression of the androgen receptor (AR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) genes in the brains of male and females. To do so, we cloned túngara-specific sequences for AR, ERα, and ERβ, determined their distribution in the brain, and then quantified their expression in areas that are important in sexual communication. We found that AR, ERα, and ERβ were expressed in the pallium, limbic forebrain (preoptic area, hypothalamus, nucleus accumbens, amygdala, septum, striatum), parts of the thalamus, and the auditory midbrain (torus semicircularis). Males and females had a similar distribution of AR and ER expression, but expression levels differed in some brain regions. In the auditory midbrain, females had higher ERα and ERβ expression than males, whereas males had higher AR expression than females. In the forebrain, females had higher AR expression than males in the ventral hypothalamus and medial pallium (homolog to hippocampus), whereas males had higher ERα expression in the medial pallium. In the preoptic area, striatum, and septum, males and females had similar levels of AR and ER expression. Our results suggest that sex steroid hormones have sexually dimorphic effects on auditory processing, sexual motivation, and possibly memory and, therefore, have important implications for sexual communication in this system.