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In the 1930s, Eugen Steinach's group found that estradiol induces lordosis in castrated rats and reduces the threshold dose of testosterone that is necessary for the induction of ejaculation, and that estradiol-treated intact rats display lordosis as well as mounting and ejaculation. The bisexual, estrogen-sensitive male had been demonstrated. Another major, albeit contrasting, discovery was made in the 1950s, when William Young's group reported that male guinea pigs and prenatally testosterone-treated female guinea pigs are relatively insensitive to estrogen when tested for lordosis as adults. Reduced estrogen sensitivity was part of the new concept of organization of the neural tissues mediating the sexual behavior of females into tissues similar to those of males. The importance of neural organization by early androgen stimulation was realized immediately and led to the discovery of a variety of sex differences in the brains of adult animals. By contrast, the importance of the metabolism of testosterone into estrogen in the male was recognized only after a delay. While the finding that males are sensitive to estrogen was based on Bernhard Zondek's discovery in 1934 that testosterone is metabolized into estrogen in males, the finding that males are insensitive to estrogen was based on the hypothesis that testosterone-male sexual behavior is the typical relationship in the male. It is suggested that this difference in theoretical framework explains the discrepancies in some of the reported results.

Serum levels of androgen were higher during the late part of the light phase of the light : darkness (LD) cycle than during the late part of the dark phase during three consecutive days in intact male rats. The serum concentration of androgen in blood samples obtained at hourly intervals from individual male rats fluctuated markedly with occasionally as much as a tenfold difference between the highest and lowest values. Evidence was presented that endogenous pulses in the concentrations of androgen in serum of male rats occur during the late part of the light phase and the early and middle parts of the dark phase of the LD cycle. Induction of sexual behaviour by injections of testosterone in castrated rats depended on the time of injection, and the period of maximum behavioural sensitivity to testosterone coincided with the time of the LD cycle when pulses in androgen levels in serum normally occurred in intact rats. Injection of testosterone produced extremely high concentrations of androgen in serum within 0.5 h of injection but these levels declined rapidly thereafter. Testosterone implants, which produced low levels of androgen that did not vary with the LD cycle, were considerably more potent than testosterone injections in stimulating sexual behaviour in castrated rats.

Male rats were selected for showing or not showing lordosis in response to manual stimulation. They were subsequently tested for mounting behavior with receptive females and for lordosis behavior in response to manual stimulation and to male mounting. Males showing lordosis as intacts displayed this behavior more readily following castration or castration and treatment with estradiol benzoate or testosterone propionate than males which did not show lordosis before castration. No group differences in mounting behavior could be detected under any of the endocrine conditions studied. It is suggested that the neural mechanisms mediated mounting and lordosis are dissociated and that individual differences in the occurrence of lordosis in male rats are due to differences in neural sensitivity to estrogen.

Masculine sexual behaviour was induced in castrated sexually inactive but experienced male rats by testosterone-filled constant-release implants or daily injections of the synthetic androgen 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R 1881), which resists metabolism by target organs. Feminization of the hepatic androgen metabolism by subcutaneous implantation of osmotic minipumps, which delivered a constant amount of human GH, did not affect the behavioural response of castrated rats to testosterone. Testosterone implants were only minimally effective in inducing male behaviour in ovariectomized female rats, but R 1881 was as effective in stimulating male behaviour in females as in males. Testosterone-treated but not R 1881-treated females showed pronounced female sexual behaviour in response to progesterone treatment despite the absence of measureable amounts of oestradiol-17 beta in peripheral blood. The results provide evidence that masculine sexual behaviour can be activated by an androgen in the absence of oestrogenic stimulation and suggest that the sex difference in the behavioural response to testosterone may be due to a sex difference in the metabolism of androgens by the brain.

Castrated male rats treated daily with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 20 mg/kg) started to display mounts, intromissions and ejaculations more rapidly in response to daily treatment with testosterone propionate (TP, 0.15 mg/kg) than NaCl-treated rats. Daily treatment with the catecholamine (CA) synthesis inhibitor alpha-methyl-p-tyrosine (alpha-MT, 20 mg/kg) had no effect on the behavioral response to subsequent TP treatment. The acceleration of TP-induced sexual behavior by PCPA pretreatment was inhibited by pretreatment with DL-5-HTP (20 mg/kg) but not with L-DOPA (12.5 mg/kg). Analyses of brain monoamines showed that the PCPA treatment reduced brain 5-HT levels and produced a marked inhibition of the 5-HT synthesis. The 5-HTP treatment restored brain 5-HT levels to normal. Daily treatment with PCPA also reduced brain CA levels and inhibited the CA synthesis but these biochemical effects were not related to the effects of PCPA on sexual behavior. Daily treatment with PCPA (40 mg/kg for 12 days) or treatment with 126 mg/kg PCPA for 3 days induced the complete pattern of sexual behavior in 5 of 9 and 19 of 30 castrated rats respectively without concurrent TP treatment. It is suggested that 5-HT exerts a modulating influence on sexual behavior in male rats.

Sexual behaviour and the function of the accessory sexual glands were studied in castrated rabbits injected with testosterone benzoate (TB), oestradiol benzoate (OEB), dihydrotestosterone benzoate (DHTB) or OEB in combination with DHTB. Testosterone benzoate (1 mg daily for 90 days) stimulated the sexual behaviour more than any of the other steroids. The combination of OEB (0-33 mg) and DHTB (1 mg) was no more effective than either of these steroids given alone. The function of the accessory sexual glands was stimulated to a level comparable to that of intact animals given TB. Dihydrotestosterone benzoate was, however, not very effective in this respect. Oestradiol benzoate alone or in combination with DHTB caused hypertrophy and very low secretory activity of the seminal vesicles. These results suggest that testosterone itself is active both in the brain and in the accessory sexual glands in rabbits. This is in contrast to the rat, in which aromatization to oestradiol in the brain and reduction to DHT in the periphery seems to be important.

The synthesis of catecholamines and serotonin in the brains of castrated male rats was analyzed at either various times after castration or at various ages. It was found that (a) castration of rats at 50 days or later causes an increase in brain monoamine synthesis, and (b) this phenomenon was not observed until 20 days after castration. The increase in brain monoamine synthesis following castration was counteracted by treatment with testosterone, thus relating the biochemical consequences of castration with changed hormonal conditions of the animal. It is suggested that testosterone exerts an inhibitory influence on monoamine synthesis.