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.     

Peripheral and central androgenic stimulation of sexual behaviour of castrated male rats

The effects of androgens on the maintenance and restoration of sexual behaviour (mounts, intromissions and ejaculations) of castrated male rats were studied. In the maintenance study the rats were treated during 5 weeks, starting one day following castration. Testosterone propionate maintained sexual behaviour at an almost normal level. The androgenoestrogen intermediate 19-hydroxytestosterone propionate was unable to prevent the decline in the number of ejaculations over the weeks although this hormone maintained the post-ejaculatory refractory period in those rats that ejaculated and also maintained normal sexual latencies. In the restoration study administration of testosterone propionate during 7 weeks to long-term castrated rats restored sexual behaviour to normal. 19-Hydroxytestosterone propionate treated rats displayed mounts but no other signs of sexual behaviour. The 5alpha-reduced androgen dihydrotestosterone propionate did not restore sexual behaviour. Testosterone propionate and dihydrotestosterone propionate stimulated peripheral target organs; 19-hydroxytestosterone propionate was ineffective in this respect. It has been suggested that testosterone might stimulate sexual behaviour in rats in two ways, i.e., via its aromatization to oestradiol in the brain, andy by stimulating growth of peripheral tissues via its 5alpha-reduction to dihydrotestosterone. In support for this view we have found that the combination of 19-hydroxytestosterone propionate and dihydrotestosterone propionate was effective in restoring the full pattern of sexual behaviour in castrated male rats.     

Olfactory recognition in the male hamster: effect of non-aromatizable androgens, 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (R 1881) and 5 alpha-dihydrotestosterone, in combination with oestrogen

Intact male hamsters show olfactory behaviour (sniffing and licking) to novel females. After exposure to female vaginal secretions, they show less sniffing towards a novel female if she does not match previously encountered odours (Steel, 1984). Male hamsters, castrated and injected s.c. with various steroids, were tested for the amount of sniffing they directed towards novel and mismatching females. 5 alpha-Dihydrotestosterone propionate (DHTP), 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R1881) and oestradiol benzoate alone did not influence olfactory behaviour, while testosterone propionate (TP), DHTP plus oestradiol and R1881 plus oestradiol all increased sniffing to a novel female over the levels shown by saline-treated, castrated controls. Our results also indicated that only the aromatizable androgen (TP) or non-aromatizable androgens DHTP and R1881, in combination with oestradiol, reduced sniffing directed to a mismatching female after exposure to vaginal odour. We conclude that both androgenic and oestrogenic actions are required not only for olfactory behaviour, but also for olfactory recognition as indicated by a reduction in sniffing directed towards mismatching females. This suggests that aromatization of testosterone may be involved in the control of olfactory processes associated with reproductive behaviour.     

Effects of anti-oestrogen treatment of neonatal male rats on lordosis behaviour and mounting behaviour in the adult

Male rats were treated daily with 100 microgram of the anti-oestrogen ethamoxytriphetol (MER-25) or oil during the first 10 days of life and tested for lordosis behaviour and mounting behaviour as intact adults, after castration and after castration and oestradiol benzoate or testosterone propionate treatment. The MER-25-treated rats showed higher levels of lordosis behaviour than oil-treated rats in all four treatment groups. Under each of these endocrine conditions, except after castration alone, the MER-25-treated rats showed a reduced capacity to ejaculate. Treatment of the neonatal rat with MER-25 reduced body weight in adulthood but did not change the weight of the accessory sexual glands, the testes, the number of cornified papillae on the glans penis or plasma testosterone concentrations during development. The response of the accessory sexual glands and cornified papillae on the glans penis to treatment with oestradiol benzoate or testosterone propionate after castration in adulthood was unaffected by treatment with MER-25. It is suggested that formation of oestrogen in the neonatal male rat brain from testosterone in the circulation inhibits the capacity to show lordosis behaviour and facilitates the capacity to ejaculate in response to ejaculate in response to gonadal hormone treatment in adulthood.     

Androgenic control of the harderian gland in the male golden hamster.

In the golden hamster, there are marked sex differences in the Harderian gland. Male glands (which are heavier than female glands) possess two cell forms (Type I and Type II cells); female glands only exhibit the former. Female (but not male) glands contain large amounts of porphyrin, which are readily visible as solid depositions within the lumina. The weight, histology and porphyrin content of the Harderian gland was examined in intact adult male hamsters and in male hamsters castrated for 1,2 or 8 months. Castration resulted in a significant reduction in the weight of the gland, the disappearance of Type II cells, and the presence in the gland of solid porphyrin accretions. The levels of copro- and (especially) protoporphyrin were greatly increased. These changes were more marked with time after castration. When the ability of diverse androgens (testosterone, 5alpha-dihydrotestosterone, androst-4-ene-3,17-dione (androstenedione), dehydroepiandrosterone and androsterone) to prevent these changes was tested, testosterone and androstenedione maintained glandular weight. All the androgens maintained normal frequencies of Type II cells and all except dehydroepiandrosterone prevented deposition of porphyrin. The potencies of the various androgens in maintaining normal Harderian gland morphology and activity are compared with their effects on other somatic variables and sexual behaviour.     

Testicular hormones and intermale aggressive behaviour in the presence of a female rat

A hypothesis was examined that increased levels of available testicular hormones are responsible for the increased aggressiveness of males in the presence of a female. In the first of two experiments intact male rats were injected with the androgen antagonist flutamide before exposure to oestrous, dioestrous or no females. Consistent with the hypothesis, flutamide-injected males were less aggressive than the respective control males which had been injected with oil alone. Yet the antiandrogen did not fully block the increased aggressiveness between males exposed to an oestrous female. In experiment 2 the aggressive behaviours of male rats in the presence of an oestrous female were observed after castration and restoration therapy with different amounts of testosterone propionate (TP). Neither a physiological amount (200 micrograms) nor an unusually large amount (800 micrograms) to TP could adequately mimic the effects of a gonadally intact male exposed to a sexually receptive female. These data suggest that differences in androgens available to target tissues influence aggressiveness among males exposed to a female. However, there are other factors involved, presumably the chronic morphological-physiological-behavioural changes that are provoked by copulatory experience.     

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.     

Effects of sex steroids on aggressive behavior of adult male Japanese quail

We found that the order of aggressiveness of adult male Japanese quail determined by paired fighting was not correlated with plasma testosterone level, plasma LH level, size of cloacal protrusion, testicular weight, nor body weight. Injections of testosterone into lower-ranked individuals did not elevate their ranks of aggressiveness. Aggressive behavior was lost after castration. Injections of testosterone, androstenedione, and estradiol-17β restored aggressive behavior in castrated males. The order of aggressiveness of these hormone-injected castrated birds was identical to the order observed before castration. Administration of individually different doses of testosterone did not change the order. Injections with 5α- and 5β-dihydrotestosterone did not restore aggressive behavior in castrated males. These results are consistent with the hypothesis that aggressive behavior in adult male Japanese quail, as well as their sexual behavior, is induced by estradiol-17β converted by aromatase in the brain from testosterone. However, no correlation seems to exist between the endogenous or exogenous testosterone level and the order of aggressiveness.     

Photoperiodic regulation of copulatory behaviour in the male hamster

The influence of daylength on copulatory behaviour was assessed by comparing male hamsters exposed to long or short photoperiods (14 or 2 h light/24 h). Copulation declined in animals transferred from long to short days; 13 out of 14 hamsters ceased to ejaculate within 9 weeks and many no longer intromitted in tests with sexually receptive female hamsters. The decline in copulation in hamsters experiencing short days was associated with atrophy of the gonads and flank glands. Behavioural changes in these animals were far more gradual than those observed in hamsters after surgical castration. There was significantly more mating behaviour in tests during the subjective night of the hamsters than during their subjective day. Exogenous testosterone was more effective in restoring copulation in castrated hamsters exposed to long days than in castrated animals experiencing short days. This suggests that in short days the substrate for copulatory behaviour is relatively refractory to androgens. Photoperiodically mediated changes in behaviour, physiology and morphology may each contribute directly to the reproductive quiescence presumed to occur in the field during the short days of autumn and winter.     

Differences in blood levels of androgens in female talapoin monkeys related to their social status

Serum testosterone and androstenedione levels were lower in the subordinate female talapoin monkeys of four social groups than either dominant or intermediate-ranking females. This was found in both intact or ovariectomized (oestrogen-treated) animals, which suggests that androgen from the adrenals contributed to this rank-related endocrine effect. These differences disappeared when the females were housed singly, levels in all animals becoming similar to those in subordinates in the group cage. There were no rank-related differences in progesterone levels during either the follicular or luteal phase of the cycle in intact females, or in those of ovariectomized females of different rank, but cortisol was highest in dominant group-living animals in these experiments. Significant correlations were found between androgen levels in group-living females and the amount of sexual interest shown in them by males; the amount of aggressive interaction involving each female did not correlate with her androgen levels. Social rank is defined according to the direction, not the amount, of aggression. These findings suggest that the social hierarchy regulates androgen levels in these female monkeys; there may also be effects on the ability of females to respond to their own, or to administered, androgen. Similar findings have been made previously in male talapoins. Since androgens fill a critical role in the sexual behaviour of both sexes in primates, this may be a neuroendocrine mechanism of general significance relating behaviour to social rank.     

Neonatal exposure to delta 9-tetrahydrocannabinol enhances sexual responses in the adult male mouse

From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 microliters sesame oil, 0.5 mg tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol (delta 9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 microliters oil. Additionally, the pups were given 20 microliter oil, 10 micrograms testosterone or 20 micrograms testosterone in 20 microliter oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone-filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0.5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed.     

Sexual dimorphism of the chromatographic profiles of I-compounds (endogenous deoxyribonucleic acid modifications) in rat liver

DNA of all tissues studied thus far in untreated mammals contains as yet structurally unidentified, covalent modifications termed I (indigenous)-compounds, which are detectable by the 32P postlabeling assay for DNA adducts and increase with age. The purpose of this study was to determine the effects of sex, gonadectomy, and androgen administration on I-compound profiles and levels in order to gain insight into the factors involved in the biosynthesis of these DNA modifications. Liver DNA from various groups of 6-month-old Sprague-Dawley rats (untreated or gonadectomized males and females; animals with or without gonadectomy treated with testosterone propionate) was analyzed by a nuclease P1-enhanced version of the 32P postlabeling assay. Hepatic I-compound profiles of untreated animals exhibited pronounced sexual dimorphism. In addition to a number of I-compounds that differed quantitatively between sexes, 7 female-specific and 1 male-specific I-compounds were observed. In female rats, the total level amounted to 112 I-compounds in 10(9) DNA nucleotides and exceeded the level in males by 3-fold. Castration feminized and ovariectomy masculinized I-compound profiles and levels. Neonatal testosterone propionate failed to restore the male pattern of I-compounds lost by neonatal castration, so that an androgen-imprinting mechanism did not appear to be involved in the maintenance of the male I-compound phenotype and the suppression of the female pattern. Testosterone propionate administered to intact female animals lowered total I-compound levels significantly. The results indicate that estrogens play a dominant role in regulating sex-dependent formation of I-compounds in rat liver. The dependence of I-compound formation on both age and sex hormones suggests that the levels of these DNA modifications are developmentally controlled.     

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.     

Elevated beta-human chorionic gonadotropin and testosterone in cord serum of male infants of diabetic mothers

Leydig cell hyperplasia is a common histological finding in male infants of diabetic mothers. The functional correlates of this histological finding were investigated by measuring beta hCG, testosterone, androstenedione, dihydrotestosterone, and progesterone in mixed cord serum of male and female infants of diabetic mothers (n = 40) and normal mothers (n = 40) at term. Male and female infants of diabetic mothers had significantly higher cord serum beta hCG levels than male and female controls. Male infants of diabetic mothers had significantly higher cord serum testosterone concentrations than male controls, female controls, and female infants of diabetic mothers. Cord serum testosterone concentrations were similar in female infants of diabetic mothers and female controls. In the male infants of diabetic mothers, there was a significant positive correlation between beta hCG and testosterone (r = 0.64; P less than 0.01). There was no significant correlation between beta hCG and testosterone in the male controls (r = -0.15; P = NS). There was no significant difference in cord serum dihydrotestosterone in any group tested. Cord serum progesterone was significantly higher in the males than in the females. Cord serum androstenedione was lower in the infants of diabetic mothers than in the controls. This study suggests that the Leydig cell hyperplasia found in male infants of diabetic mothers is due, in part, to elevated concentrations of hCG and is accompanied by elevated testosterone concentrations in the fetal compartment.     

Effects of hyperprolactinaemia on male sexual behaviour in the golden hamster and mouse

In the male rat, hyperprolactinaemia is associated with significant reductions in plasma LH and FSH levels and in several measures of copulatory behaviour. In contrast to this situation, experimental induction of hyperprolactinaemia in male mice and hamsters is associated with an increase in plasma gonadotrophin levels. It was therefore of interest to determine the effects of hyperprolactinaemia on the copulatory behaviour of these animals. Hyperprolactinaemia was induced by transplantation of pituitaries from adult females and sexual behaviour was tested in the presence of ovariectomized, oestrogen- and progesterone-treated females. Because hyperprolactinaemia increases plasma testosterone levels in intact male hamsters, the animals were castrated and implanted with testosterone-filled silicone elastomer capsules before induction of hyperprolactinaemia. In mice of two inbred strains, DBA/2J and C57BL/6Bg, hyperprolactinaemia appeared to stimulate male sexual behaviour as shown by a significant increase in the proportion of animals mating (C57BL/6) and a significant decrease in mount (DBA/2J) and intromission (C57BL/6Bg and DBA/2J) latencies. Similarly, hyperprolactinaemia did not suppress male copulatory behaviour in the hamster. In contrast, in two experiments in which the animals were tested three times for sexual behaviour, mount or intromission latencies were significantly reduced in pituitary-grafted, as compared with sham-operated males, in the first of the tests. Thus, in the mouse and the golden hamster, experimentally induced chronic hyperprolactinaemia stimulates both gonadotrophin release and male copulatory behaviour. These observations, together with the association of suppressive effects of hyperprolactinaemia on plasma LH and FSH levels and on sexual behaviour in the male rat, suggest the possible existence of a common mechanism underlying both endocrine and behavioural effects of hyperprolactinaemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex steroids in the umbilical circulation of fetal rhesus monkeys from the time of gonadal differentiation

Male rhesus monkey fetuses have significantly more testosterone (T) in their circulation than females on days 35--50 of gestation (P less than 0.01; n = 6 males and 6 females). However, we found no sex differences for androstenedione (delta 4). T concentrations remained significantly higher in male fetuses than in females later in gestation, e.g. days 79--84, 100--133, and 140--160. Levels of delta 4 differed between the sexes only on days 79--84, and dihydrotestosterone concentrations were significantly higher in male fetuses than in females on days 100--133 and 140--163. The fact that delta 4 concentrations were not different between the sexes at the earliest period studied (days 35--50) indicates that systemic concentrations of this hormone in the fetus probably are not important for sexual differentiation, especially of the central nervous system. Quantification of three steroids (T, delta 4, and dihydrotestosterone) in umbilical arterial and venous plasma from five male and nine female fetuses (days 35--100) revealed significant arterial/venous differences only for T in males (arterial greater than venous). These data, which suggest that fetal testes secrete T during morphological differentiation, lend credence to the hypothesis that endogenous T partially regulates sexual differentiation.     

Hypophysectomy prevents the castration-induced increase in porphyrin concentrations in the harderian glands of the male golden hamster: a possible role for prolactin.

The Harderian glands of golden hamsters contain high concentrations of porphyrin pigments, with female hamsters having considerably higher porphyrin concentrations than males. Castration of male hamsters leads to a rapid increase in porphyrin concentrations; testosterone treatment of females has the opposite effect, suggesting a central role for androgens in inhibiting the realization of high porphyrin concentrations by this organ. Previous studies in our laboratories have shown, however, that administration of a dopamine agonist to castrated hamsters prevents the normal increase in Harderian porphyrins from occurring. This suggests that prolactin is necessary for low androgen levels to lead to maximal increases in Harderian porphyrin concentrations. The present study tested the hypothesis that prolactin is involved in the control of Harderian porphyrin levels in the golden hamster. Although hypophysectomy of male hamsters reduced serum testosterone to levels in castrated hamsters, the resultant increase in Harderian porphyrin concentrations was much less than that seen after a similar period of castration. Furthermore, combining the two procedures (castration and hypophysectomy) also led to a blunted increase in Harderian porphyrin, suggesting that a pituitary hormone is necessary for low testosterone levels to lead to increased porphyrins. Evidence that this pituitary hormone is prolactin comes from the observations that eliminating all pituitary hormones except prolactin, by severing the connection of the pituitary with the hypothalamus or transplanting the pituitary to a distant site (beneath the kidney capsule) led to greatly augmented Harderian porphyrin levels, in intact or castrated male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effect of androgen on the synthesis of proteinase F in the male mouse submandibular gland

Androgenic regulation of one of the esteroproteinases (proteinase F) in the mouse submandibular gland was studied using specific antiserum. In contrast to esteroproteinases such as proteinases A, D or P-esterase, proteinase F content in male but not in female mice was increased by gonadectomy and decreased by the injection of various androgens. In-vivo incorporation of [3H]leucine into proteinase F in males was increased after castration and decreased by the injection of testosterone propionate; androgens inhibited the de-novo synthesis of proteinase F in male mice. The dose-response curves for testosterone propionate and time-courses following castration or after the injection of testosterone propionate were reciprocal between proteinase F and total esteroproteinase activity. Proteinase F, like other esteroproteinases in the submandibular gland of the mouse, was localized in granular convoluted tubular cells. These data indicate that granular convoluted tubular cells of the male mouse submandibular gland synthesize both androgen-inducible proteinases and androgen-inhibitory proteinase (proteinase F).     

Penile development is initiated in the tammar wallaby pouch young during the period when 5alpha-androstane-3alpha,17beta-diol is secreted by the testes

Virilization of the urogenital tract is under the control of testicular androgens in all mammals. In tammar young, prostate differentiation begins between d 20 and d 40 under the control of the testicular androgen 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol), but uncertainties exist about the control of penile development. We performed longitudinal studies up to d 150 of pouch life to define normal penile development and the effects of androgen administration and castration. In control animals the male phallus was longer than the female phallus by d 48. Closure of the urethra in males begins around d 60 and continues to at least d 150. Administration of supraphysiological doses of testosterone to females caused penile development equivalent to that of the male and also induced partial closure of the urethral groove by d 150. Castration of male pouch young at d 25 prevented penile development, whereas the penis in males castrated at d 40, 80, or 120 had partial closure of the urethral groove. Administration of 5alpha-adiol to females from d 20-40 also caused partial closure of the urethral groove and some growth of the phallus at d 150, whereas 5alpha-adiol treatment from d 40-80 or 80-120 caused some penile growth but had little effect on urethral development. These findings, together with the fact that we found no sex differences in plasma levels of testosterone, dihydrotestosterone, 5alpha-adiol, dehydroepiandrosterone, or androstenedione from d 51-227, clearly indicate that the action of 5alpha-adiol between d 20 and 40 imprints later differentiation of the male penis.     

Synergism between bovine seminal plasma extract and testosterone propionate in suppressing serum concentrations of gonadotrophins in acutely castrated rats: a role for inhibin

The rise in concentrations of FSH and LH in serum seen 24 h after castration was suppressed by the administration of an extract of bull seminal plasma or testosterone propionate at the time of castration. Whereas testosterone propionate preferentially suppressed LH, the seminal plasma extract suppressed FSH and LH equally. Small doses of bull seminal plasma extract and testosterone, that had little effect separately, acted synergistically to supress levels of FSH and LH to those found in intact animals, while combinations of larger doses had little further effect. This selective interaction suggests how inhibin and testosterone might together regulate concentrations of FSH and LH in the blood of the male rat.