Effects of aromatizable androgens on aggressive behaviour among rats (rattus norvegicus)

Three experiments were used to tests the applicability of the aromatization hypothesis of androgen action to aggressive behaviour among Norway rats. In Expt 1, administration of testosterone propionate was highly effective in restoring aggressive behaviour to castrated rats while 17 beta-hydroxy-5 alpha-androstan-3-one was of intermediate effectiveness. Of the steriods tested in Expt 2, androstenedione and testosterone were highly effective, 17 beta, 19-dihydroxyandrost-4-en-3-one was of intermediate effectiveness and cholesterol was ineffective. The results of Expt 3 indicated that treatment with testosterone or oestradiol both resulted in increased aggression while treatment with (5 alpha,17 beta)-17,19-bis(acetyloxy)-andostan-3-one diacetate (5 alpha-19-hydroxytestosterone) was without effect. Androgens which were aromatizable and could be 5 alpha reduced, i.e. testosterone, testosterone propionate and androstenedione, were highly effective in restoring aggressive behaviour; however, two other steroids, 5 alpha,19-hydroxytestosterone which is 5 alpha reduced, and 19-hydroxytestosterone, which can be aromatized, were respectively of low or medium effectiveness on behaviour. However, oestradiol, which did not maintain sexual development of accessory glands, was highly effective in the restoration of aggressive behaviour. Since the behaviourally active steroids in the present experiments were not only those predicted by the aromatization hypothesis, it is proposed that several steroids are capable of activating aggressive behaviour and that the aromatization hypothesis does not adequately explain the hormonal basis of aggressive behaviour among Norway rats.     

Changes in aggressive and sexual responsiveness of male golden hamsters after neonatal androgen administration

On day 1 after birth, male golden hamsters received either 300 microng of an androgen (testosterone propionate, testosterone, dihydrotestosterone or androstenedione) in 0-03 ml arachis oil, or oil alone. As intact adults, their aggressiveness towards unreceptive females was measured. After this, all animals were castrated. At least 3 weeks after the operation all animals received oestradiol benzoate (10 microng) + progesterone (500 microng), after which their capacity to show patterns of female sexual behaviour towards a stud male was tested. Control hamsters which had received oil as neonates showed less aggression than the females with which they interacted; these controls also readily assumed lordosis after castration and priming with ovarian steroids. Conversely, animals which had received testosterone propionate or androstenedione neonatally were as aggressive as the female hamsters, and showed a markedly decreased ability to display lordotic behaviour after castration. The behaviour of male hamsters which received testosterone or dihydrotestosterone was unaffected. Thus, at the level of treatment used, increased aggressiveness appeared to co-vary with a decreased capacity to show female sexual behaviour patterns. However, within each treatment there was little evidence of such a relationship at the level of the individual animal.     

Minimal effects of 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (R1881) on sexual behaviour in prepubertally castrated rams

Ten adult prepubertally castrated rams were injected with 5 alpha-dihydrotestosterone propionate (DHTP; 20 mg/day) for 3 weeks to stimulate genital development. Thereafter, half of the sheep were injected with testosterone (100 mg/day) for a further 4 weeks, while the remainder received the same dose of 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (methyltrienolone; R1881). All the animals were tested for sexual behaviour on 15 occasions with ovariectomized ewes in which oestrous behaviour was induced by injections of 50 micrograms oestradiol-17 beta benzoate at 4- to 5-day intervals. Behavioural tests were of 10 min duration and were carried out thrice weekly over a 5-week period, starting in the final week of DHTP treatment. Animals treated with testosterone showed a highly significant increase in courtship behaviour (tongue-flicks; lunges and nudges) after only four daily injections and this level of activity was maintained to the end of the experiment. However, the incidence of courtship activity in sheep treated with R1881 was similar to that recorded during the period of DHTP treatment. All animals given testosterone displayed mounts with pelvic thrusts and erections, and achieved intromission with ejaculation. These activities remained significantly more frequent than in sheep treated with R1881, starting from tests 9, 8 and 12 respectively. Four of the five individuals in the group given R1881 showed occasional mounts with thrusts, three showed sporadic erections and one sheep intromitted in the final test. These results indicate that, in contrast to the rat, R1881 has only very weak effects on sexual behaviour in the castrated ram.     

The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment

The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to delta 4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5 alpha-androstane-3,17-dione (5 alpha AD). Despite the low testosterone values, DHT and 5 alpha AD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5 alpha-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids.     

Plasma vasopressin and oxytocin levels in intact goats and in castrated goats given testosterone

Oxytocin, vasopressin, cortisol and testosterone levels in the plasma were measured by radioimmunoassay in intact male goats as well as in prepubertally castrated goats injected daily, for 2 weeks, with oil vehicle and then, for 4 weeks, with testosterone propionate in oil to study the influence of gonadal steroids on posterior pituitary hormones. Packed cell volume, plasma osmolality and sodium concentration were also measured in all blood samples. Plasma levels of oxytocin, vasopressin and cortisol were similar in the intact and oil-injected castrated goats. Testosterone treatment significantly increased plasma levels of oxytocin (P less than 0.01) in castrated goats but the increased levels were similar to those seen in the intact goats at the same time of year. Plasma levels of cortisol and vasopressin were unaffected by testosterone propionate treatment, whereas packed cell volume was significantly decreased (P less than 0.01). Testosterone treatment of castrated male goats appears not to have any action on pituitary hormones and oxytocin increases in the spring in both intact and castrated male goats.     

Differential effects of gonadectomy on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour in rams

Castrated sheep were used to study the effects of gonadectomy on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour. In the first experiment serum LH and FSH concentrations were determined in intact rams, recently castrated (2 days and 3 weeks) and long-term castrated animals (greater than 2 years, wethers) during intravenous testosterone infusion at physiological and supraphysiological levels. In intact rams, testosterone infusions effectively suppressed serum LH whilst FSH levels were suppressed only after prolonged infusion at the supraphysiological dose. Recently castrated sheep, which had higher gonadotrophin levels than intact rams, were less sensitive to testosterone feedback. Neither rate of testosterone infusion had any effect on the raised gonadotrophin levels in wethers. In a second experiment gonadotrophin concentrations and mating behaviour were determined in wethers bearing subdermal polydimethylsiloxane implants of testosterone, dihydrotestosterone and oestradiol. Testosterone implants stimulated mating behaviour in all wethers but suppressed gonadotrophins in only a proportion (three out of seven) of the animals. Both oestradiol and dihydrotestosterone suppressed LH and FSH in all wethers, whilst oestradiol, but not dihydrotestosterone, also stimulated mating behaviour. The present findings indicate that testosterone imposes continuing negative feedback on gonadotrophin secretion and that changes in the gonadotrophin regulatory system, which lead eventually to a loss in sensitivity to testosterone feedback, develop soon after gonadectomy. The results also provide the first direct evidence that longterm gonadectomy in male sheep has differential effects on sensitivity to testosterone of brain centres associated with gonadotrophin negative feedback and with mating behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)     

Androgenic and estrogenic control of the self-priming effect of LHRH in the castrated male rat

Intact pubertal or young adult male rats release more luteinizing hormone in response to luteinizing hormone releasing hormone (LHRH) if pretreated with LHRH than if pretreated with saline. Castrated male rats do not show this self-priming effect of LHRH. In an attempt to determine the testicular factor responsible for the maintenance of the self-priming effect, pubertal male rats were castrated and implanted subcutaneously with various sizes of testosterone-filled Silastic capsules. Control rats were castrated or sham-operated and implanted with empty capsules. Rats were examined for a self-priming effect 4 days later. All sizes of testosterone capsules used maintained the self-priming effect. Three additional experiments were performed to determine the ability of dihydrotestosterone, estradiol and androstenedione to maintain a self-priming effect. The following groups were included in each experiment: castrated plus empty capsule, castrated plus testosterone-filled capsule, castrated plus one of two sizes of capsule filled with the steroid of interest, and sham-operated plus empty capsule. Dihydrotestosterone and estradiol, but not androstenedione were capable of maintaining a self-priming effect. Since it is generally considered that dihydrotestosterone cannot be aromatized to estrogen, this action of estradiol and dihydrotestosterone is probably accomplished by different mechanisms.     

Suppression of the development of female hamster behaviour by implants of testosterone and non-aromatizable androgens administered neonatally.

Testosterone in its free form, and dihydrotestosterone (DHT) and androsterone, both androgens which are not aromatizable to oestrogen, injected in oil during the neonatal period have been reported not to modify the development of female sexual behaviour. This failure might be due to the short period of activity of these substances when injected in liquid vehicles. In the current study, a Silastic pellet containing 9% of its weight of testosterone, androsterone, or DHT was implanted subcutaneously in 42 female and 38 neonatally castrated male hamsters on day 2 of life and removed on day 10. Pellets of pure Silastic were implanted in 36 control animals. Males were gonadectomized on day 5 and females on day 45. Female sexual behaviour induced by oestradiol benzoate and progesterone was measured in a series of 10-min mating tests with vigorous males, starting at 55 days of age. The duration of lordosis was consistently reduced below control levels in females implanted with testosterone, DHT, and androsterone, and in males, with testosterone and DHT. Thus the free form of testosterone, and some non-aromatizable androgens, when present for a sufficiently long period after birth, can permanently suppress development of female reproductive behaviour.     

Activation of sexual behaviour in castrated rats: the role of oestradiol

Sexual behaviour was induced in castrated male rats with oestradiol-17 beta- or testosterone-filled constant-release implants. Testosterone-induced sexual behaviour was unaffected by treatment with the 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4-MA; 16.7 mg/day) but treatment with the aromatization inhibitor 1,4,6-androstatriene-3,17-dione (ATD; 10 mg/day) prevented testosterone from inducing the behaviour. Sexual behaviour could be activated in castrated rats treated with testosterone plus ATD by treatment with 4-MA or with implants filled with a low dose of oestradiol. Lordosis behaviour induced in ovariectomized rats with testosterone-filled implants and progesterone was blocked by ATD treatment and could not be activated with 4-MA but oestradiol implants restored the display of lordosis in the testosterone plus ATD-treated females. 4-MA inhibited the in-vitro formation of [14C]5 alpha-dihydrotestosterone from [14C]testosterone by combined preoptic and hypothalamic tissue at all doses tested and a high dose of oestradiol exerted a similar effect. The results suggest that androgen aromatization is required for testosterone-activated female sexual behaviour but not for testosterone-activated male sexual behaviour. It is suggested that oestradiol normally acts to control the sexual behaviour of male rats by modifying neural androgen metabolism.     

Role of gonadal and adrenal steroids in the impairment of the male rat's sexual behaviour by hyperprolactinaemia

The sexual behaviour of male rats, castrated and testosterone-implanted, declined following induction of hyperprolactinaemia by domperidone. Treatment with oestradiol benzoate did not reverse this effect, and may have accentuated it. Oestradiol also amplified domperidone-induced hyperprolactinaemia. Testosterone or dihydrotestosterone (DHT) apparently delayed, but did not prevent, the gradual deterioration in sexual behaviour (prolonged ejaculation latencies) induced by domperidone, but this effect was not confirmed statistically. Adrenalectomy, followed by cortisol replacement, failed to prevent the behavioural effects of hyperprolactinaemia. No consistent changes in serum progesterone or corticosterone could be found in hyperprolactinaemic rats in which the adrenals had not been removed. In vitro formation of DHT from precursor testosterone was reduced in the amygdalae of hyperprolactinaemic rats, but not in the hypothalamus or caudal spinal cord. Oestradiol cytosol binding was unchanged in all brain areas, except for a small but significant increase in the anterior hypothalamus. These results do not support a role for altered adrenal activity in determining the effects of high levels of prolactin on sexual behaviour. There is evidence for an impaired formation of DHT in the brain, but this may account for only part of the behavioural changes observed. It is possible that the major effect of prolactin lies in neural systems directly responsive to it, rather than in altered steroid secretion or metabolism.     

Comparison of androgen levels in normal males (Gallus domesticus) and in males made sexually inactive by embryonic exposure to testosterone propionate.

Testosterone propionate (TP) administered to chicken embryos on the third day of embryonic development will markedly inhibit the development of normal male sexual behavior. This study was conducted to monitor the testosterone and dihydrotestosterone (DHT) levels in the serum of these TP males. Eggs from a New Hampshire strain of chickens were dipped on the third day of incubation in 2% TP solution. Blood samples were collected from TP and control males when they were 12, 16, 20, and 24 weeks old. Radioimmunoassay was used to measure testosterone and DHT in all serum samples. Mating behavior was tested when the birds were 24 weeks old. Testosterone and DHT concentrations were significantly lower in the serum of TP birds than in control birds. Testicular and pituitary gland weights were also decreased significantly in TP males. Mating behaviors of TP birds were markedly inhibited. In explaining the failure of TP males to mate we have entertained a threshold response theory (failure of the mating center to respond), a concentration theory (too low a concentration of incubating androgens), and a barrier theory (failure of the androgens to reach the hypothalamic mating center).     

Effects of testosterone on spermatogenesis and luteinizing hormone release in Japanese quail

Testosterone or testosterone propionate was administered to Japanese quail (Coturnix coturnix japonica) via intraperitoneal Silastic capsules to assess the role of these androgens on spermatogenesis and luteinizing hormone (LH) release. Testosterone was released from Silastic capsules at relatively constant rates and in direct proportion to capsule length. Increasing lengths of testosterone-filled Silastic capsules induced and maintained differential increments in plasma testosterone titers and caused a concomitant decline in plasma immunoreactive LH levels in castrated quail. In intact birds, testosterone implants ranging between 40 and 320 mm caused a graded reduction in paired testis weight, spermatogenic activity, and circulating LH titers, but plasma testosterone levels remained within the range noted in intact control birds. Marked increases in plasma testosterone concentrations were noted in intact birds receiving 600- and 1200-mm testosterone or 500-mm testosterone propionate implants. Importantly, paired testis weight and the relative number of germ cells were maintained at near normal levels when plasma testosterone titers were raised about 18-fold above normal. The results indicate that the continuous administration of small amounts of testosterone (about 1 mg/day) suppressed spermatogenesis by inhibiting LH release and that spermatogenesis was maintained during the continuous administration of large amounts of testosterone (about 12 mg/day) even though LH secretion remained suppressed. The present findings support the hypothesis that testosterone exerts a differential effect on the quail testis that depends, in part, upon the amount of androgen administered.     

Testosterone metabolites do not participate in the control of hypothalamic LH-releasing hormone

To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormone (LHRH) in orchidectomized rats might be explained by the conversion of the hormone into either its 5 alpha-reduced or oestrogenic metabolites, testosterone, 5 alpha-androstan-17 beta-ol-3-one (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) (2 mg/rat per day for 6 days) and oestradiol (0.1, 0.5, 1.0 and 5.0 micrograms/rat per day for 6 days) were injected into castrated male rats. After 6 days the rats were killed and serum LH levels and intrahypothalamic LHRH stores measured using specific radioimmunoassay procedures. Testosterone and its 5 alpha-reduced metabolites were used in either the free alcohol or the propionate form (dipropionates in the case of the diols); oestradiol was used as oestradiol-17 beta or in the benzoate form. Treatment with testosterone, DHT, 3 alpha-diol and 3 beta-diol resulted in a significant decrease in serum LH levels; all the 5 alpha-reduced testosterone derivatives were more effective than testosterone in this respect. Testosterone and DHT propionates suppressed LH release following orchidectomy totally; 3 alpha-diol and 3 beta-diol dipropionates were less effective. Testosterone increased intrahypothalamic LHRH stores, this effect being much higher after testosterone propionate, i.e. when intrahypothalamic LHRH stores were restored to pre-castration levels. None of the 5 alpha-reduced steroids was capable of modifying the low intrahypothalamic levels of LHRH found following orchidectomy; only 3 alpha-diol dipropionate exhibited some activity, but this was much lower than that of testosterone propionate. Oestradiol-17 beta was totally ineffective in decreasing serum LH in orchidectomized animals; in contrast, oestradiol benzoate progressively decreased serum LH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nuclear accumulation of androgens in perfused rat accessory sex organs and testes.

The uptake of androgens into the nuclei of caput epididymis, ventral prostate, seminal vesicle and testis was studied by recirculating physiological and pharmacological concentrations of [3H]testosterone in an artificial medium through the lower half (hemicorpus) of castrated or hypophysectomized rats. The accumulation of dihydrotestosterone in accessory sex organ nuclei was saturable, inhibited by perfusion of excess testosterone or cyproterone acetate, and associated with binding to 3S salt-extractable molecules. In castrated preparations the mean saturation levels (pmol/mg DNA) were different in the three organs: seminal vesicle, 2.8; ventral prostate, 1.8; caput epididymis, 0.9. The saturation level was significantly lower in ventral prostate of hypophysectomized rats (1.2) treated with testosterone to regenerate the accessory sex organs. Testosterone was the major nuclear androgen in the testes of mature hypophysectomized preparations perfused with testosterone. Although there was a large amount of nonspecific accumulation, testosterone binding to 3S molecules was shown by sucrose gradient centrifugation. Binding of dihydrotestosterone to 3S molecules in testicular nuclei was also demonstrated. The ratio of dihydrotestosterone to testosterone was different in immature and mature testicular nuclei and was altered by treatments known to affect testicular 5 alpha-reductase activity. The results suggest that in rat accessory sex organs and immature testis the major active androgen is dihydrotestosterone, whereas in mature testis it is testosterone. The shift in the predominant nuclear androgen in the testis from dihydrotestosterone to testosterone is most simply explained by the maturational change in 5 alpha-reductase activity.     

Androgen-estrogen synergy in rat levator ani muscle: glucose-6-phosphate dehydrogenase

The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17 beta alone was ineffective. Combined treatment with estradiol-17 beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.     

Blockade of testosterone-induced mounting behavior in the male rat with intracranial application of the aromatization inhibitor, androst-1,4,6,-triene-3,17-dione.

Propylene glycol (glycol) solutions containing either testosterone (T) or estradiol (E2) were infused directly into the preoptic area (POA) of longterm castrated rats in order to reinstate male copulatory behavior. In addition, castrated males were administered T or E2 in the POA in combination with a steroid that has been shown to block the aromatization of testosterone to estradiol, androst-1,4,6-triene-3,17-dione (ATD). The facilitatory action of testosterone on mounting behavior was blocked when it was given in combination with ATD. Animals treated in the POA with glycol +T, glycol +E2 or ATD + E2 all showed significant increases in mounting behavior over preimplant levels. There was no significant rise in the number of intromissions or ejaculations in any of the hypothesis that, at least for mounting behavior, aromatization is necessary for the stimulation of male sexual behavior by testosterone.     

The effect of castration and testosterone replacement on specific proteins and androgen levels of the rat epididymis.

The normal weight increase of the epididymis during sexual maturation and its maintenance through adulthood were found to be dependent on the provision of androgens. Binding of [3H]dihydrotestosterone (DHT) to the epididymal 8S cytoplasmic receptor gradually decreased after castration to become undetectable after 25 days. Binding to the androgen binding protein (ABP) was absent 4 days after castration and was not reinduced by 3 weeks of testosterone (T) administration. Unilateral castration for periods of up to 27 days showed the disappearance of ABP with preservation of the 8S receptor on the castrated side, indicating a testicular source for ABP and the epididymal origin of the 8S receptor. The tissue concentrations of T and DHT in the epididymis became undetectable 30 days after castration and were restored to normal values by administration of testosterone in large doses (1.5 mg/100 g BW). Similar results were obtained in rats castrated at 10 days of age and injected with testosterone until 60 days old. The ratio DHT/T was depressed in the castrate and increased with testosterone treatment. The protein content of the epididymis (mg of protein/g wet weight) was also found to be influenced by androgens. Our results show evidence of some mechanisms involved in the trophic effect of androgens upon the epididymis and suggest the possible androgenic control of epididymal 5alpha-reductase activity. They also indicate that a testicular factor is required for the maintenance of the 8S cytoplasmic androgen receptor. It is not known whether this factor is testosterone or some other testicular secretion.     

Correlation of catecholamine levels in the bed nucleus of the stria terminalis and reduced sexual behavior in middle-aged male rats

The correlation between dopamine (DA) and norepinephrine (NE) levels in the bed nucleus of the stria terminalis (BNST) and male sexual behavior was examined in middle-aged rats. Male rats (18-19 months) were divided into: (a) Group MIE, consisting of rats showing mounts, intromissions, and ejaculations; (b) Group MI, composed of rats showing mounts and intromissions, but no ejaculation; and (c) Group NC, consisting of noncopulators. Young adult rats (4-5 months) displaying complete copulatory behavior were used as the control. Tissue levels of DA, NE, and DA metabolites in the BNST were measured by high-pressure liquid chromatography. DA, but not NE, levels in MIE rats were significantly lower than those in young controls. DA and NE levels in MIE rats were significantly higher than those in NC rats. These results suggest that DA and NE in the BNST might play an important role in the control of male sexual behavior in middle-aged rats.     

Low serum testosterone/dihydrotestosterone ratio in patients with pancreatic carcinoma

Serum testosterone, its metabolite 5 alpha-dihydrotestosterone, and the testosterone/dihydrotestosterone ratio were investigated in 22 male patients with proven pancreatic cancer, and compared with values from male patients with chronic pancreatitis (n = 21) and with nonpancreatic gastrointestinal tumors (n = 19). Testosterone and the testosterone/dihydrotestosterone ratio were significantly lower (p less than 0.001) in the pancreatic cancer group when they were compared with the other two groups. There was no significant difference in the dihydrotestosterone values between cancer groups. A testosterone/dihydrotestosterone ratio of less than 5 clearly distinguished most of the patients (20/22) with cancer of the pancreas from those with other tumors or chronic pancreatitis. The results suggest an alteration in the serum androgen profile in these patients. Therefore, the testosterone/dihydrotestosterone ratio could be a useful marker in the diagnosis of pancreatic carcinoma in male patients.     

Sexual behaviour in castrated rabbits treated with testosterone, oestradiol, dihydrotestosterone or oestradiol in combination with dihydrotestosterone.

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.