James E. Shryne

Evidence for a morphological sex difference within the medial preoptic area of the rat brain.

The present report demonstrates the existence of a marked sexual difference in the volume of an intensely staining cellular component of the medial preoptic nucleus (MPON) of the rat. Moreover, this sexual dimorphism is shown to be independent of several specific hormonal conditions in the adult, but significantly influenced, perhaps determined, by the perinatal hormone environment. Adult rats were gonadectomized and sacrificed 2 or 5-6 weeks later, or sacrificed after gonadectomy and priming with estradiol benzoate (2 microgram/day x 3) and 500 microgram progesterone, or testosterone propionate (TP, 500 microgram/day x 14), or the ingestion of propylthiouracil (0.15% of the diet) for one month, or following water deprivation for 24 h. These treatments did not affect the sexual dimorphism in the MPON and, in all groups, nuclear volume in the male animals was significantly greater than that of females whether nuclear volume was expressed in absolute terms or relative to brain weight. On the other hand, the volume of the MPON of the adult male castrated neonatally was significantly reduced when compared to that of the male castrated at the time of weaning, i.e. after the period of sexual differentiation of the brain. Consistent with the view that this nuclear region undergoes sexual differentiation is the fact that the volume of the MPON was significantly greater in female rats injected with 1 mg TP on day 4 of life than in oil-treated females. More subtle sex differences in the volume of the suprachiasmatic nucleus were also detected, as were several treatment effects. Although these differences may fall within the error of the analytical procedure, it is possible that hormone- or sex-dependent morphological differences exist elsewhere in the brain. Nevertheless, the gross sexual dimorphism in the MPON clearly demonstrates a possible morphological basis for the sexual differentiation of brain function.

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.

Termination of the hormone-sensitive period for differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat brain is several-fold larger in males than in females. The volume of the SDN-POA can be influenced significantly by the hormone milieu during early postnatal life. The purpose of the present study was to identify when termination of the sensitive period occurs during which exogenous androgen administration influences SDN-POA volume in males gonadectomized on the first day of postnatal life (fales) or intact females. Analysis of the SDN-POA in fales showed that testosterone propionate (TP, 500 micrograms) treatment on days 2, 3, 4, or 5, significantly increased its volume over values from oil-treated fales. In contrast, TP treatment in fales on days 6, 7, or 8, failed to increase SDN-POA volume. A similar pattern was observed in females treated with TP. Females treated with TP (500 micrograms) on days 2, 3, 4, or 5, showed a significant increase in SDN-POA volume compared to the values from oil-injected animals, while the same TP treatment in females on days 6, 7, or 8, resulted in no such enhancement. The absolute and relative change in SDN-POA volume following postnatal androgen treatment is greater in males than in females. We conclude that (1) SDN-POA development is sensitive to hormone action through postnatal day 5 and then abruptly becomes insensitive to this dosage of TP, and (2) although the temporal pattern of the response is similar in males and females, androgen exposure postnatally results in a consistently greater increase in the male SDN-POA volume than in the females. This greater response may be due to exposure prenatally to endogenous androgen in males.

Differentiation of the sexually dimorphic nucleus in the preoptic area of the rat brain is determined by the perinatal hormone environment

The volume of a sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) their SDN-POA developed equivalent in size to that of normal males. The results indicate that the gross morphological sex difference in SDN-POA volume is exclusively controlled by the hormonal environment during the critical period of sexual brain differentiation.

Septal lesions: Effects on lordosis behavior and pattern of gonadotropin release

Abstract Septal lesions increase behavioral responsiveness to estrogen of male, female, and androgen-sterilized female (ASF) rats as measured by lordosis behavior. Male and ASF animals normally show low levels of female sexual receptivity when compared to normal female rats. However, the level of female sexual behavior in male and ASF rats with septal lesions is comparable to that of highly receptive female rats. Progesterone facilitates the estrogen-induced female sexual behavior of female, but not male or ASF, animals. Andrenalectomy had no effect on the increased behavioral sensitivity to estrogen induced by septal lesions. Amygdala lesions, comparable in size to septal lesions, did not facilitate female sexual behavior. The male or female pattern of gonadotropin release is not affected by septal lesions, indicating a disassociation between the regulation of gonadotropin release and sexual behavior. Since septal lesions facilitate lordosis behavior in rats, the septal region appears to exert a tonic inhibition on female sexual behavior.

Differentiation of the Sexually Dimorphic Nucleus in the Preoptic Area of the Rat Brain Is Inhibited by Postnatal Treatment with an Estrogen Antagonist

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in adult male rats that in adult females. This sex difference in brain structure was previously shown to develop under the influence of androgenic and estrogenic hormones during the perinatal period. We here report that treatment of newborn male and female rats with the estrogen antagonist tamoxifen significantly inhibited growth and differentiation of the SDN-POA in both sexes and it resulted in permanent anovulatory sterility in females. The findings suggest (a) that testicular androgens exert their growth promoting activity on SDN-POA development only after being converted into estrogens, and (b) that also in the female rat structural and possibly functional brain differentiation is under estrogenic control.

Structural Sexual Dimorphisms in the Anteroventral Periventricular Nucleus of the Rat Hypothalamus Are Sensitive to Gonadal Steroids Perinatally, but Develop Peripubertally

The volume of the anteroventral periventricular nucleus (AVPv) of the rat hypothalamus is larger in females than in males. A preliminary study from this laboratory found that this sexual dimorphism develops between days 30 and 91. The present study was designed to confirm and extend these findings and to determine the role of endogenous gonadal steroids in the development of the AVPv postnatally. The results indicate that the sexual dimorphism in AVPv volume arises between days 30 and 40 and that the length of the nucleus becomes sexually dimorphic between days 60 and 80. Additionally, both AVPv volume and length increased between days 30 and 80 in females. Castration of male rats on the day of birth sex-reversed AVPv volume in adulthood and AVPv length was sex-reversed by castration of males 5 days after birth; ovariectomy of females at these ages had no effect on either parameter. Moreover, in both males and females, AVPv volume and length were unaffected by gonadectomy at later ages. That the AVPv appears to be influenced by testicular hormones neonatally, but changes structurally around the time of puberty in females, clearly challenges current concepts of sexual differentiation that limit the process to the early postnatal period.

Pre- and Postnatal Influence of an Estrogen Antagonist and an Androgen Antagonist on Differentiation of the Sexually Dimorphic Nucleus of the Preoptic Area in Male and Female Rats

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is severalfold larger in adult male rats than in adult females. This sex difference in brain structure was previously shown to develop under the influence of androgenic and estrogenic hormones during the perinatal period. We tried to clarify the differential role played by androgens and estrogens during development and differentiation of the SDN-POA by treating male and female rats during an extended pre- and postnatal period either with the estrogen antagonist tamoxifen or with the androgen antagonist cyproterone acetate. Treatment with tamoxifen did not alter serum levels of testosterone in male rats during the perinatal period, but it inhibited development and differentiation of the SDN-POA. Pre- and postnatal treatment of male rats with cyproterone acetate resulted in female phenotypic appearance, but it had no influence on differentiation of the SDN-POA. Perinatal treatment of female rats with tamoxifen resulted in permanent anovulatory sterility, but did not influence SDN-POA differentiation. Treatment of female rats with cyproterone acetate had no influence on SDN-POA differentiation or on the capacity to ovulate. Since pre- and postnatal treatment of male rats with cyproterone acetate is known from previous studies to femenize sexual behavior patterns and to retain the mode for cyclic gonadotropin release, and since the same treatment did not influence differentiation of the SDN-POA in the present study, it may be concluded that the SDN-POA is not directly involved in the control of female sexual behavior and in the control of the gonadotropic hormone release pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of septal lesions on behavioral sensitivity of female rats to gonadal hormones

Abstract Spayed female rats were given bilateral septal lesions or a sham operation and 3 wk later tested for hormone-induced female sexual behavior. When primed with 0.5, 1.0, or 2.0 μg of estradiol benzoate (EB) per day for 3 days and tested for lordosis behavior on the fourth day, animals with septal lesions showed a positive dose-related increase in mean lordosis quotient (LQ), whereas control animals showed a low mean LQ for all doses of EB. After priming with a low dose of EB (0.5 μg/day for 3 days), progesterone administration prior to behavior testing on day 4 produced a comparable facilitation in LQ for both septal-lesioned and sham-operated animals. When treated for 3 days with either 50 or 150 μg of testosterone propionate (TP) and given progesterone prior to behavior testing on day 4, female rats with septal lesions showed a higher mean LQ than sham-operated rats. Thus, septal lesions increase the behavioral sensitivity of female rats to both EB and TP as measured by female sexual behavior, but do not appear to alter the responsiveness of animals to progesterone.

The inhibition of steroid-induced sexual behavior by intrahypothalamic actinomycin-D

Abstract Lordosis behavior can be elicited in the ovariectomized rat after treatment with estradiol benzoate (EB) and progesterone (P) injections, but the EB must act for an extended period before P can facilitate this behavior. The possibility that this action of EB involves the stimulation of RNA or protein synthesis was tested by implanting actinomycin D (Act-D) directly into the preoptic area, one probable site of estrogen action. A total dose of 0.18 μg Act-D in bilateral cocoa butter pellets significantly inhibited lordosis behavior when implanted 12 hr after the injection of 3 μg. but not 15 μg EB. Implantation of this dose of Act-D subcutaneously, or intrahypothalamically 32 hr after EB injection, was without effect. Act-D placed in the ventromedial hypothalamus also suppressed lordosis, but implants in the caudate nucleus were without effect. At the time of the behavioral tests the animals were in excellent condition as determined by calculation of a health score, and no physical lesions were evident at the site of the implants. However, it was impossible to test the reversibility of this suppression of lordosis behavior since the animals became ill and many died within 1–2 weeks of implantation. The present results are consistent with, but not proof of, the concept that RNA synthesis may be essential for steroidinduced sexual behavior.