Lynwood G. Clemens

Prenatal endogenous androgenic influences on masculine sexual behavior and genital morphology in male and female rats.

Female rats located near a male during uterine development showed increased frequencies of male-like behavior as adults and virilization of genital morphology. These changes in behavior and morphology were blocked by prenatal treatment with the anti-androgen, Flutamide.

Neurohormonal control of male sexual behavior.

Testosterone not only sustains male sexual behavior in castrated male rats and induces male sexual responses in the female but also increases female responses (Whalen and Hardy, 1970; Pfaff, 1970). Similarly, estrogen facilitates sexual receptivity in both males and females and increases male sexual behavior in the gonadectomized rat (Pfaff, 1970).

Projections of the paraventricular nucleus of the hypothalamus to the sexually dimorphic lumbosacral region of the spinal cord

Lumbar regions L5-L6 of the spinal cord of the male rat contain the sexually dimorphic motor nuclei, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN), which innervate perineal muscles, the bulbocavernosus and the ischiocavernosus, respectively. This neuromuscular system controls penile reflexes which are essential to male reproductive success. Oxytocin has been shown to induce penile reflexes and the site of action for these effects is the PVN. Since PVN is known to project to cervical and thoracic levels of spinal cord, the present study examined projections of the PVN to the L5-L6 region of the spinal cord. WGA-HRP was injected into the region of L5-L6, aimed at the SNB and DLN and their dendritic extents, in intact male, castrated male and female rats. WGA-HRP-labelled cells bodies were found in the parvocellular subnuclei of PVN, as well as regions of the lateral hypothalamus and the dorsal area of the hypothalamus. These results demonstrate that the PVN projects to lumbar levels of the spinal cord that are sexually dimorphic and androgen-dependent. This suggests that PVN may modulate the activity of these motoneurons.

Alteration of muscarinic binding in specific brain areas following estrogen treatment

Systemic administration of estradiol benzoate (EB) to ovariectomized female rats significantly altered cholinergic muscarinic binding of [3H]quinuclidinyl benzilate in discrete brain regions. Specifically, EB increased muscarinic binding in the medial basal hypothalamus (MBH) and decreased muscarinic binding in the medial preoptic area (POA). These alterations were dose-dependent and appeared to reflect changes in the number of muscarinic binding sites. Treatment with EB failed to significantly affect binding in several control areas in females or in the MBH and POA of males.

Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats.

Some environmental contaminants have the potential to affect humans or animals by mimicking the effects of hormones. Bisphenol A (BPA) is a weak estrogen agonist when tested using in vitro or in vivo bioassays. In addition to the well documented effects of estrogens on reproductive functions, ovarian hormones also have salient effects on mammalian energy balance and feeding behavior. In this study, we investigated the effects of BPA on body weight and food intake of ovariectomized adult female rats. Treatment with doses of 4 or 5 mg/day for 15 days resulted in a significant reduction of body weight gain with no reduction in food intake. A dose of 1 mg/day did not affect feeding or weight gain. BPA was detected in the blood, brain and adipose tissues of the BPA-treated animals but not in the vehicle control group. There was a preferential concentration of BPA in brown adipose tissue. These results indicate that BPA can affect energy balance and that brown adipose tissue may be a primary tissue into which BPA accumulates in mammals.

Feminine sexual behavior in rats enhanced by prenatal inhibition of androgen aromatization

Abstract Male and female rats were exposed to the aromatization inhibitor 1,4,6-androstatriene-3, 17-dione (ATD) in utero via prenatal injections to the pregnant mother. In adulthood, lordosis behavior was measured in response to ovarian hormones. Males and females exposed prenatally to ATD showed enhanced lordosis behavior in response to estrogen alone and in response to estrogen plus progesterone when compared to controls. These data lend further support to the idea of a prenatal, androgen-sensitive phase of sexual differentiation in which defeminization normally occurs in both male and female rats. Further, these data support the concept that androgen aromatization is an important process in this defeminization.

Masculinization of the female golden hamster by neonatal treatment with androgen or estrogen

Abstract Female hamsters which received treatment with testosterone, testosterone propionate, or diethylstilbestrol on Days 2–4 of postnatal life displayed mounting behavior after treatment in adulthood with testosterone propionate. Virtually no mounting was observed in animals treated neonatally with androsterone or control substances. Peripheral morphology was masculinized by androsterone, testosterone, and testosterone propionate but not by diethylstilbestrol or control substances. These results are consistent with the hypothesis that development of male sexual behavior is dependent upon the presence of estrogen or androgen which can be metabolized to estrogen during sexual differentiation. Dissociation of the effects of neonatal treatment upon behavior from those upon peripheral morphology suggests that the induction of masculine behavior results from a central neural hormone action.

Neonatal androgen and adult sexual behavior in the golden hamster

Abstract Two experiments assessed the influence of neonatal hormones on adult sexual behavior in the golden hamster. In Experiment 1 males were castrated or sham-operated on Day 1, 6 or 25 post partum. Sham-operated males were castrated at 40 days of age. Males castrated on Day 1 following birth and receiving adult testosterone propionate (TP) injections failed to show increased mounting toward a receptive stimulus female, while males castrated at later ages (6 days of age or older) responded to adult TP with an augmented mount frequency. Day 1 male castrates were also significantly more responsive to injections of exogenous ovarian hormones (estradiol benzoate and progesterone) than were males castrated at 6 days of age or older. In a second experiment males and females received neonatal injections of either TP or oil and were tested as adults for both masculine and feminine behavior patterns. Females receiving TP on either Day 2 or 4 post partum showed low levels of feminine response patterns (lordosis) and increased mounting behavior. Females receiving TP on Day 10 or oil on Day 2, 4 or 10 post partum showed high levels of lordosis and did not mount. Cyclicity was absent in TP Day 2 and some TP Day 4 females but the remaining females showed 4-day vaginal and behavioral cycles. Both masculine and feminine behaviors in response to exogenous adult hormones were depressed in males receiving TP on Day 2 or 4.

MPOA lesions affect female pacing of copulation in rats.

This study examined the effects of electrolytic and ibotenic acid (IA) lesions of the medial preoptic area (MPOA) on the temporal pattern of female sexual behavior in the laboratory rat. Both electrolytic and IA MPOA lesions significantly increased the females latency to return to the male after an intromission or an ejaculation, thereby decreasing the percentage of time spent with a male. Both types of MPOA lesions significantly increased the percentage of times the female left the males chamber following intromissions. These results demonstrate that neurons in the MPOA regulate the females temporal copulatory behavior, and the authors suggest that they do so by virtue of their response to vaginocervical stimulation. Studies of female pacing draw attention to parallels between male and female sexual behaviors, including the possibility that they are regulated by similar neural substrates in the MPOA.

Aromatization and the induction of male sexual behavior in male, female, and androgenized female hamsters.

Abstract Eight weeks after gonadectomy male, female, and androgenized [10 μg testosterone propionate (TP), 24 hr after birth] female hamsters were given daily treatment with: 150 μg dihydrotestosterone (DHT), 5 μg estradiol benzoate (EB), 150 μg DHT + 5 μg EB, 150 μg DHT + 1 μg EB, 30 μg DHT + 5 μg EB, 30 μg DHT + 1 μg EB, or the oil vehicle. Treatment of castrated male hamsters with 5 μg EB fully restored mounting but relatively few of these animals intromitted and none ejaculated. Treatment with 150 μg DHT restored all components of male sexual behavior but only in a small proportion of the males. Combined treatment with EB and DHT restored mounts, intromissions, and ejaculations in the majority of the males. Although as little as 30 μg DHT + 1 μg EB restored the full complement of male behavior, the males which received 150 μg DHT + 5 μg EB or 150 μg DHT + 1 μg EB required fewer intromissions to achieve ejaculation than the males which received 30 μg DHT + either dose of EB. The response of the androgenized females was similar to that of the males except that the androgenized females had lower intromission rates and none ejaculated. Relatively few of the nonandrogenized females responded to EB and DHT treatment and those that did mounted only a few times each test. These results demonstrate that both EB and DHT can stimulate male sexual behavior in the hamster and that the sensitivity to EB and DHT for copulatory behavior is determined by early postnatal androgen exposure.