Flutamide blocks the self-priming effect of luteinizing hormone-releasing hormone in pubertal male rats

Castration of pubertal or young adult male rats eliminates the self-priming effect of luteinizing hormone-releasing hormone on luteinizing hormone secretion. Testosterone, dihydrotestosterone, or estradiol will maintain this effect in castrated animals. In order to explore the mechanism by which both dihydrotestosterone and estradiol are capable of maintaining the effect, intact rats as well as castrated animals implanted with testosterone capsules were treated with the antiandrogen Flutamide. In both intact animals and castrated rats bearing testosterone-filled Silastic capsules, Flutamide blocked the self-priming effect. These data suggest that the androgen receptor is of primary importance in the maintenance of the self-priming effect.     

Sex hormones and susceptibility of the rat to paracoccidioidomycosis

The development of intraperitoneal paracoccidioidomycosis was studied in groups of female and male rats: a) U nder normal conditions (intacts), b) After castration and c) After castration but submitted to a treatment with, respectively, testosterone and estradiol.The criterion of susceptibility to infection was based on: 1) Spontaneous mortality of the animals and 2) Number of metastatic pulmonary lesions.The results showed that: the unique deaths and the more severe pulmonary lesions were found among the intact females, representing the animals most susceptible to the infection in these experiments; the intact females showed more numerous lesions than the castrated; the intact males had less lesions than the castrated, and than those castrated which were treated with estradiol.     

Endocrine status affects bladder size and postvoid residual urinary volume in mice

Urine is one of the major media for intraspecific chemical communication in mice. The urination pattern is dependent both on the mice's hormonal and social status. The urination pattern and the morphology of the urinary tract were examined in mice following hormonal manipulations. In the first experiment, we compared pairs of intact and castrated males: intact males urinated earlier when exposed to a new environment, with a greater number of drops that were smaller than those of castrated males. In the second experiment, groups of intact males, castrated, testosterone-supplemented castrated, and isolated intact males were compared. The micturition pattern of isolated intact males consisted of numerous small droplets of urine, with a high volume of urine retained in the bladder after voiding. This also applied to grouped intact males and testosterone-treated castrated mice, while castrated mice voided a larger fraction of bladder content. Bladder weight was higher in intact males and testosterone-treated castrated males, as compared to castrated males. In the third experiment, ovary-intact and testosterone-treated intact females were compared. Testosterone-treated ovary-intact females retained a larger quantity of urine in the bladder and also had a larger bladder compared to ovary-intact females. Testosterone thus induces the morphological modifications of the urinary tract necessary for the dominant male urination pattern, which is an increase in postvoid urinary residual volume and bladder weight. As evidenced from the comparison of histological sections from intact, castrated, and testosterone-treated castrated males, the increase in bladder weight was mainly due to the bladder muscular mass.     

MICROBODIES IN EXPERIMENTALLY ALTERED CELLS : II. The Relationship of Microbody Proliferation to Endocrine Glands

The liver cells of intact male rats given ethyl-α-p-chlorophenoxyisobutyrate (CPIB) characteristically show a marked increase in microbodies and in catalase activity, while those of intact female rats do not. In castrated males given estradiol benzoate and CPIB the increase in catalase activity and microbody proliferation is abolished, while in castrated females given testosterone propionate and CPIB the livers show a marked increase in microbodies and in catalase activity. No sex difference in microbody and catalase response is apparent in fetal and neonatal rats. Both sexes show a sharp rise in catalase activity on the day of birth, with a rapid decline at 5 days after birth. Thyroidectomy abolishes the hypolipidemic effect of CPIB in rats, but microbody proliferation and increase in catalase activity persists in thyroidectomized male rats, indicating that microbody proliferation can be independent of hypolipidemia. Adrenalectomy does not alter appreciably the microbody-catalase response to CPIB. These experiments demonstrate that (1) in adult rats, hepatic microbody proliferation is dependent to a significant degree upon male sex hormone but is largely independent of thyroid or adrenal gland hormones; (2) hepatic microbody proliferation is independent of the hypolipidemic effect of CPIB; (3) displacement of thyroxine from serum protein may not be sufficient cause for stimulation of microbody formation.     

Adaptation to chronic hypobaric hypoxia and sexual hormones

The role of the gonads and their hormones on body weight was studied in rats of both sexes submitted to chronic hypoxia and their controls at sea level atmospheric pressure. Intact rats were exposed to either 4 700 or 6 000 m simulated altitude in a hypopressure chamber. Castrated rats and castrated rats daily injected with either 0.5 mg of testosterone or 20 microgram of estradiol or the vehicle, were exposed to the higher altitude. The rat weight was recorded for a period of at least eight weeks. All groups of hypoxic male animals increased their weight significantly less than the controls at sea level. Also in castrated females and in castrated injected with testosterone or the vehicle the same pattern of weight curves was observed. On the contrary, groups of intact females and castrated females injected with estradiol did not show significant differences between hypoxic and control animals. Only in a group of smaller intact females (50-80 g) the body weight increase was significantly diminished by exposure to either 4 700 or 6 000 m simulated altitude.     

Estrogen-activated sexual behavior in male rats

Daily injections of 100 μg estradiol benzoate activated the whole pattern of sexual behavior in castrated sexually experienced male rats. If compared to rats treated daily with 100 μg testosterone propionate, the estrogen-treated males tended to have longer latencies and more mounts and intromissions prior to ejaculation. Fifty micrograms of estradiol benzoate stimulated the display of mounts and intromissions in prepuberally castrated male rats. No peripheral effects of the estrogen treatment were noted. These results suggest that estrogen has central “androgen-like” effects, but no such effects in the periphery. Estrogen treatment (5, 50, and 200 μg/kg for 3 weeks) of intact sexually experienced male rats resulted in testicular atrophy and loss of body weight, but had no significant effects on the sexual behavior.     

Testosterone and estradiol produce different effects on cognitive performance in male rats

The effects of castration and hormone treatment on cognitive performance were evaluated in male rats. Castrated animals received either testosterone or estradiol and were compared with gonadally intact animals and with castrated controls. Results revealed a dissociation between the effects of testosterone and estradiol on cognitive performance in male rats. Specifically, estradiol enhanced acquisition of a delayed matching-to-position spatial task, similar to previously published observations in females. In contrast, neither castration nor testosterone treatment had any significant effect on acquisition of the delayed matching-to-position task, but did appear to affect delay-dependent working memory. None of the treatments had any significant effect on acquisition of a configural association negative patterning task, suggesting that effects on the delayed matching-to-position task were not due to effects on motivational factors. These data demonstrate that, as in females, gonadal hormones influence cognitive performance in males and suggest that estradiol and testosterone affect distinct cognitive domains.     

Influence of sex and gonadal hormones on rat-liver and carcass lipids during the development of an essential fatty acid deficiency

1. Groups of intact male and female rats and castrated rats injected with oestradiol or testosterone were given a diet containing hydrogenated coconut oil for 9 weeks, and at intervals the amounts and fatty acid compositions of the carcass and liver lipids were determined. 2. Male rats grew faster and larger, and exhibited typical external essential fatty acid deficiency symptoms sooner than did females. Testosterone-treated castrated male rats were similar to males, and oestradiol-injected castrated male rats resembled females. 3. Intact females maintained a higher linoleic acid concentration in their carcass than did males. Total amounts of carcass linoleic acid remained similar for all groups, only 200mg. being removed in 9 weeks regardless of body size. 4. The amounts of total cholesteryl esters were independent of liver size. They were higher in males and testosterone-treated castrated male rats than in females and oestrogen-treated castrated male rats. 5. Phospholipids represented about 80% of the liver lipids. The total amounts of the phospholipid linoleic acid and arachidonic acid were similar for all groups regardless of liver size, and were not affected appreciably by the deficiency. Females and oestrogen-treated castrated male rats maintained a higher proportion of phospholipid arachidonic acid for longer periods than did their male counterparts. Both the total amounts and the proportions of eicosatrienoic acid and palmitic acid were higher in males than in females. 6. Supplementation of the essential fatty acid-deficient diet with linoleic acid caused a rapid loss of eicosatrienoic acid and palmitic acid with a concomitant increase in stearic acid and arachidonic acid. 7. There were no obvious differences in the way that the essential fatty acids were metabolized or mobilized from adipose tissue of male or female rats during essential fatty acid deficiency. 8. The results indicated that the greater growth rate of the male rats caused them to require and synthesize more phospholipids than did the females. In the absence of adequate amounts of arachidonic acid, eicosatrienoic acid was substituted into the additional phospholipid. The earlier symptoms of essential fatty acid deficiency in the male rat could therefore be ascribed to the higher tissue concentrations of this unnatural phospholipid and its inability to perform the normal metabolic functions of phospholipids.     

Hormonal regulation of male reproductive behavior in the lizard Anolis sagrei: a test of the aromatization hypothesis

This study examined the hypothesis that aromatization of testosterone (T) to estradiol (E) is required to activate reproductive behavior in castrated male lizards (Anolis sagrei). Adult, reproductively active males were assigned to an intact control group or to one of four treatment groups. Treatment males were castrated and 1 week later three of the four castrated groups were implanted with subcutaneous pellets containing either 0.05 mg of E, 0.5 mg of T, or 0.5 mg of dihydrotestosterone (DHT). Two weeks after pellet implantation, males were tested with stimulus males, and 2 days later were tested with stimulus females. Behavioral tests were of 15-min duration and were videotaped. Significantly fewer E-treated castrates erected a crest in tests with stimulus males than did intact males. In tests with stimulus females, significantly fewer E-treated castrates displayed, neck-gripped, and intromitted than did intact males. Estradiol-treated castrates also showed significantly less display behavior than did intact males. However, aggressive and sexual behavior of DHT-treated castrates was not significantly different from that of intact males. The same was true for T-treated castrates with the exception that display behavior in tests with stimulus females was reduced compared to that of intact males. The results suggest that aromatization of T to E is not required for induction of androgen-dependent reproductive behavior in this lizard.     

Modulation of hepatic glucose-6-phosphate dehydrogenase activity in male and female rats by estrogen

The effect of estradiol-17 beta on the activity of glucose-6-phosphate dehydrogenase was studied in both male and female rats to further characterize the sex differences in the activity of this enzyme. Four groups of intact and castrated rats were implanted subcutaneously with graded doses (2.4, 4.8 and 7.2 micrograms/day) of pelleted estradiol in a physiologically relevant experimental system. After fourteen days the rats were sacrificed and their livers were assayed for G6PD activities. The result indicated that: (i) the enzyme activity was 3-fold higher in normal adult female than in male rats, (ii) low doses of E2 (2.4, 4.8 and 7.2 micrograms/day) increased the activity of G6PD 6-fold in castrated males and over 2-fold in female castrates as well as intact rats (iii) E2 stimulation of G6PD activity appears to be more effective in castrated males than in female rats (IV) sex difference in the activity of G6PD disappeared after treatment with E2 in castrated rats. It is concluded that the activity of G6PD in rats is markedly enhanced by low doses of E2, which appears to be largely responsible for the sex differences in the activity of this enzyme in rats.     

Aromatizable and 5alpha-reduced androgens: differentiation between central and peripheral effects on male rat sexual behavior.

Sexual behavior was observed in the 5 wk after castration in four separate experiments. In each, 50 male rats were allocated equally to the following treatment groups; intact controls; castrated controls; castrated + testosterone propionate, 75 μg/day; castrated + test steroid 1, 150 μg/day; castrated + test steroid 2, 150 μg/day. The following propionated compounds were used; dihydrotestosterone, androsterone, 3α- and 3β-androstanediols, androstenedione, androstanedione, 19-hydroxyandrostenedione, estradiol. With the exception of androstanedione, only aromatizable androgens or estrogen prevented post-castration increases in refractory period durations. However, aromatizable and 5α-reduced androgens stimulated penile spine growth. In each experiment there was a significant positive correlation between spine number and copulatory efficiency i.e., the ratio of intromission to mount frequencies.     

Effect of an anti-substance P serum on prolactin and gonadotropins in hyperprolactinemic rats

The effects of the acute injection of a rabbit anti-substance P serum (ASPS) were studied in normal rats and rats with hyperprolactinemia induced by 5-hydroxytryptophan and estradiol given as a short or chronic treatment. The anti-substance P serum decreased the release of prolactin induced by 5-hydroxytryptophan when this serotonin precursor was injected 24 h, but not 1 h, after the administration of the antiserum. ASPS reduced the hyperprolactinemia induced by short and chronic treatment with estradiol in castrated rats. This effect was observed 24 h after the injection of the antiserum. On the other hand, the injection of ASPS induced a significant decrease in LH levels in serum of intact male rats injected with 5-hydroxytryptophan 24 h after ASPS, and in castrated rats treated with short-term and chronic administration of estradiol, 24 h after the injection of the antiserum. These results suggest that substance P may have a role in the control of prolactin secretion and could play a part in the hyperprolactinemic effects of estradiol. On the other hand, substance P, under certain circumstances, may stimulate LH release.     

Effect of castration on hypothalamic testosterone metabolism in the male rat

In vitro studies were performed of hypothalamic testosterone (T) metabolism 30 days after castration of adult male rats. No changes were seen in T conversion into dihydrotesterone and estrogens in the castrated rats. Plasma T levels were decreased while plasma estradiol concentrations did not differ from those of intact controls. It was suggested that the hypothalamic T metabolism probably is not androgen dependent.     

Differential gene expression of organic anion transporters in male and female rats.

Sex-related differential gene expression of organic anion transporters (rOAT1, rOAT2, and rOAT3) in rat brain, liver, and kidney was investigated. There were no sex differences in the expression of rOAT1 mRNA. rOAT2 mRNA was abundant in the liver and weakly expressed in the kidney of male rats; however, the OAT2 gene was strongly expressed in both organs of females. The abundance of rOAT2 mRNA markedly increased in castrated male rat kidney; however, treatment of castrated male rats with testosterone led to a decrease of rOAT2 mRNA. Expression of rOAT3 mRNA in intact female rats was found in the kidney and brain, whereas in males rOAT3 mRNA was also found in the liver. rOAT3 mRNA markedly decreased in the liver of castrated male rats but increased in testosterone-treated castrated male rats. Moreover, rOAT3 mRNA increased in the hypophysectomized female rat liver, indicating that rOAT3 is an inducible isoform. The present findings suggest that sex steroids play an important role in the expression and maintenance of OAT2/3 isoforms in the rat liver and kidney. Our results provide information on the differential gene expression of OAT isoforms with sex hormone dependency.     

Use of a gonadotropin releasing hormone agonist implant as an alternative for surgical castration in male ferrets (Mustela putorius furo)

Surgical castration in ferrets has been implicated as an etiological factor in the development of hyperadrenocorticism in this species due to a castration-related increase in plasma gonadotropins. In search for a suitable alternative, the effect of treatment with the depot GnRH-agonist implant, deslorelin, on plasma testosterone concentrations and concurrent testes size, spermatogenesis, and the typical musky odor of intact male ferrets was investigated. Twenty-one male ferrets, equally divided into three groups, were either surgically castrated, received a slow release deslorelin implant or received a placebo implant. Plasma FSH and testosterone concentrations, testis size and spermatogenesis were all suppressed after the use of the deslorelin implant. The musky odor in the ferrets which had received a deslorelin implant was less compared to the ferrets which were either surgically castrated or had received a placebo implant. These results indicate that the deslorelin implant effectively prevents reproduction and the musky odor of intact male ferrets and is therefore considered a suitable alternative for surgical castration in these animals.     

Effect of neonatal castration on sex steroid receptor levels in the hypophysis of male rats

The content of estradiol and testosterone cytosolic and nuclear receptors has been studied in the pituitary body of adult male rats gonadectomized on day 1-3 after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and long- and short-term castrates had the same level of cytosolic and nuclear estrogen receptors. The number of cytoplasmic and nuclear testosterone-binding sites was identical in the pituitary body of adult intact mice and long-term castrates. Contrastingly, the concentrations of androgen cytosolic and nuclear receptors were significantly lower in neonatally castrated males compared to intact adult animals. The results obtained indicate that nuclear testosterone receptors in the pituitary body mediate negative feedback effect of androgen on the release of luteinizing hormone and that the formation of thin mechanism occurs within the first days of life.     

Effects of an estrogen antagonist,MER-25, on mounting behavior and lordosis behavior in the female rat

Four daily injections of 20 mg ethamoxytriphetol, MER-25, to intact female rats with regular 4-day estrous cycles inhibited lordosis behavior, but had no inhibitory effect on mounting behavior. Ten mg/day of MER-25 for 9 days partially antagonized the stimulatory effect of 2 μg/day of estradiol benzoate on lordosis behavior in ovariectomized female rats, but had no inhibitory effect upon mounting behavior. MER-25 (10 mg/day for 9 days) stimulated the display of mounting behavior in ovariectomized female rats. No effects of MER-25 treatment (10 mg for 10 days) comparable to those of testosterone propionate (10, 50, or 250 μg for 10 days) on testicular, seminal vesicle, or ventral prostate weights of intact male rats or on seminal vesicle or ventral prostate weights of castrated male rats were observed. The results show that MER-25 acts differently upon various estrogen sensitive behaviors in the female rat.     

Induction of progestin receptors in the mediobasal hypothalamus of gonadally intact male rats primed with estrogen in relation to display of lordosis behavior

The purpose of this study was to determine whether the effects of estrogen on lordosis behavior in the male rat were related to the number of progesterone (P) receptors in the mediobasal hypothalamus (MBH) and/or dependent on blood P concentration. Two groups of gonadally intact male rats were given five successive doses of 1.0 or 2.5 micrograms estradiol benzoate (EB) and tested for lordosis behavior with a male stimulus at the end of the treatment. One month later they were again injected with EB and sacrificed under the same temporal schedule, but they were not tested for lordosis so as to prevent any emotionally stressful effects of intermale cohabitation. The males given 2.5 micrograms EB more frequently displayed lordosis responses to male mounts than those receiving 1 microgram EB, with a parallel increase in the number of MBH P receptors. The total number of MBH P receptors also appeared to be higher in the animals that displayed lordosis responses (lordosis group) than in those which did not (no lordosis group). In contrast, the display of lordosis behavior was negatively correlated with blood P concentration. Comparing MBH P receptors and blood P values in the EB treated and in nonhormonally treated gonadally intact animals which had been selected for either ability or inability to spontaneously display lordosis behavior, we observed that (1) EB was capable of increasing the number of MBH P receptors in the male rat; and (2) in the absence of EB treatment blood P values were higher in the animals showing lordosis than in those which did not. These data are discussed with respect to observations made in castrated male rats and in ovariectomized females.     

Sexual responses of the male rat medial preoptic area and medial amygdala to estrogen II: site specific effects of selective estrogenic drugs

In the medial preoptic area (MPO) and medial amygdala (MEA), estradiol (E(2)) aromatized from testosterone (T) may act via either estrogen receptor (ER) α or ERβ to mediate mating in male rats. We tested the hypothesis that, in the MPO, ERα exclusively mediates sexual responses to E(2) by monitoring mating in four groups of castrated male rats administered dihydrotestosterone (DHT) subcutaneously and MPO implants delivering either: cholesterol, E(2), propyl pyrazole triol (PPT, ERα-agonist) or diarylpropionitrile (DPN, ER β-agonist); a fifth group of intact males served as DPN toxicity control, receiving DPN MPO implants. In a follow-up study, either 1-methyl-4-phenyl pyridinium (MPP, ERα-antagonist) or blank MPO cannulae were implanted in castrated male rats receiving T subcutaneously, whereas intact MPP toxicity controls received MPP MEA implants. PPT or E(2) MPO implants maintained mating, but cholesterol or DPN MPO implants did not. Moreover, MPP MPO implants interfered with T reinstatement of mating suggesting that, in the MPO, ERα is necessary and sufficient for mating in androgen-maintained male rats and ERβ is not sufficient. Because it is unknown which ER subtype(s) mediate sexual responses of the MEA to E(2), we examined mating following MEA implants of cholesterol, E(2), PPT or DPN in four groups of castrated male rats administered DHT subcutaneously. E(2) MEA implants maintained mounting but mating was significantly decreased in groups receiving PPT, DPN or cholesterol MEA implants suggesting that, unlike the MPO where ERα alone is essential, sexual responses of the MEA to E(2) require simultaneous interactions among multiple ER subtypes.     

性腺甾体激素对雌,雄大鼠下丘脑血管升压素mRNA水平的影响

实验用１０－１１周龄经阉割的雌、雄Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠进行。以３末端异羟基洋地黄毒甙标记的２６个碱基长的寡核苷酸作为检测探针,用核酸斑点杂交技术检测大鼠下丘脑血管升压素ｍＲＮＡ水平。在假手术对照组,雄性大鼠下丘脑ＡＶＰｍＲＮＡ水平经雌性大鼠高４５％（Ｐ〈０．０５）,血浆渗透压高于雌性大鼠（Ｐ〈０．０５）。摘除卵巢的大鼠下丘脑ＡＶＰｍＲＮＡ深恶痛绝经假手术组雌性大鼠高３０％（Ｐ〈０．０５