Activation of sexual behavior in male rats by combined subcutaneous and intracranial treatments of 5 alpha-dihydrotestosterone

When given peripherally, 5 alpha-dihydrotestosterone, the major androgenic metabolite of testosterone, is relatively less effective than testosterone in activating sexual behavior of castrated male rats. In order to test the possible central nervous system effects of dihydrotestosterone more directly, we castrated Long-Evans rats, gave them a behaviorally subthreshold dose of dihydrotestosterone placed subcutaneously in Silastic capsules (ScDHT), and then additionally treated the rats with intracranial implants of crystalline dihydrotestosterone (IcDHT, N = 12), testosterone (IcT, N = 12), or cholesterol (IcCHOL, N = 10) placed in the medial preoptic area. The peripheral ScDHT treatment maintained sexual organ weights of castrated males at levels comparable to those of intact males, but did not in itself significantly activate mating behavior. The addition of IcT or IcDHT to this treatment regimen significantly increased the number of males displaying mounting behavior, intromissions, and ejaculatory behavior (P less than 0.05) compared to males with IcCHOL implants. There were no significant differences between the group given IcT and the group given IcDHT. Results of this study support the hypothesis that the nonaromatizable androgen 5 alpha-dihydrotestosterone can act in the rat brain to influence male sexual behavior. In addition, these data lead us to suggest that the relative ineffectiveness of dihydrotestosterone versus testosterone when given systemically may reflect differences in bioavailability of these hormones to the brain following such treatment.     

Effects of exogenous steroids on androgen receptors in fetal guinea pig brain

We treated pregnant guinea pigs on Day 50 of gestation with 10 mg testosterone propionate (TP), obtaining fetuses 2, 4, 8, or 18 h later as well as after 5 days of treatment. In a second group of pregnant guinea pigs, dihydrotestosterone propionate (DHTP), estradiol benzoate (E2B), progesterone (P), or cortisol was given 2 h before obtaining fetuses. Although TP treatment elevated fetal serum T (p less than 0.05), brain cytosolic androgen receptor (ARc) content was unchanged in fetuses of either sex. In female fetuses, nuclear androgen receptors (ARn) increased 10-fold in medial-basal hypothalamus (MBH) and preoptic area (POA) at 2 and 4 h (respectively) after treatment, while fetal male ARn content was unchanged. Maternal injection of other steroids (E2B, P, or cortisol, but not DHTP) significantly increased these hormones in the fetus 2 h later (p less than 0.05). Only androgens affected fetal androgen receptor (AR) content. While TP increased ARn in female MBH, DHTP decreased ARc in fetal anterior pituitary of both sexes. In this latter case, a metabolite of DHT may mediate the effects. We conclude that T crosses the guinea pig placenta and activates ARn in POA and MBH of female fetuses; male ARn appear to be maximally occupied by endogenous T. Steroids of other classes do not induce AR responses in fetal guinea pig brain. These AR changes may represent an initial cellular mechanism in brain sexual differentiation.     

Adrenocortical function of the domestic fowl: effects of orchiectomy and androgen replacement

The effect of orchiectomy and androgen replacement on cockerel adrenocortical function was investigated. Orchiectomized cockerels (2 weeks old) were implanted with Silastic tubing containing various amounts of one of the following steroids: cholesterol, testosterone (T), androstenedione (A4), and 5 alpha-dihydrotestosterone (DHT). Birds were administered additional implants, containing doses of steroids equivalent to those of the initial implants, at 4 and 8 weeks of treatment (i.e., 6 and 10 weeks of age). Sham-operated cockerels administered empty implants served as intact controls for comparison of data. Animals were killed after 10 weeks of treatment (12 weeks old). Trunk plasma corticosterone (B) and plasma T, and B production by collagenase-isolated adrenocortical cells incubated briefly (2 hr) with or without steroidogenic agents were measured by radioimmunoassay. Orchiectomy with implantation of the inert sterol, cholesterol (hereafter referred to as orchiectomy), did not alter plasma B concentrations and did not affect basal cellular B production or cellular B production induced by a maximal steroidogenic concentration of ACTH or that maximally supported by 25-hydroxycholesterol. However, orchiectomy did lower maximal 8-bromo-cyclic AMP-induced B production by 30%. Low-implant doses of A4 (1-cm implant) and T (0.3-cm implant), that maintained comb growth, lowered plasma B concentrations by 24-42%, whereas a high-implant dose of T (3-cm implant) and all implant doses of DHT had no effect on plasma B concentrations. Thus, androgen replacement had different effects on plasma B depending on the type of androgen and the implant dose. In contrast, androgen replacement consistently suppressed basal and maximal ACTH-induced cellular B production regardless of the type of androgen. Furthermore, the degree of suppression was dose-dependent. These results suggest that the differential effect of androgen replacement on plasma B concentrations was due to differences in the clearance of circulating B and/or differences in blood volume. In addition, the present study suggests that in the absence of the testes, androgens are suppressants of adrenocortical cell function in the domestic fowl.     

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.     

Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men

The concentrations of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione (A-dione), testosterone (T) and dihydrotestosterone (DHT) have been measured before and after castration in men and two animal models, namely the rat and the guinea pig. In adult men, the pre-castration levels of plasma DHEAS and DHEA were measured at 1839 +/- 320 and 2.4 +/- 0.5 ng/ml, respectively, while in both animal models, the concentrations of these two steroids were below 0.3 ng/ml. Orchiectomy in men reduced plasma T and DHT levels from 2.9 +/- 0.1 and 0.60 +/- 0.10 to 0.42 +/- 0.21 and 0.05 +/- 0.01 ng/ml (P less than 0.01), respectively, while there was no significant effect observed on DHEAS, DHEA and A-dione levels. By contrast, castration in the rat reduced the low levels of circulating DHEA and A-dione below the detection of the radioimmunoassay (RIA) used. In castrated guinea pig, a small quantity of plasma A-dione (0.07 +/- 0.02 ng/ml) was measured while DHEA was undetectable. Moreover, in the rat and guinea pig, plasma T and DHT levels became undetectable. Following administration of the antiandrogen Flutamide for two weeks in the castrated rat and guinea pig, prostate weight was not further reduced, thus indicating that there is no significant androgenic activity left following castration of these two species. In fact, castration in the rat and guinea pig caused a decrease in prostatic levels of DHT from 4.24 +/- 0.351 and 9.42 +/- 1.43 ng/g, respectively, to undetectable levels. In men, on the other hand, the prostatic DHT levels were only inhibited from 5.24 +/- 0.59 to 2.70 +/- 1.50 ng/g, respectively. As expected, when Flutamide was administered to the rat and the guinea pig, the levels of prostatic steroids remained undetectable while, in men, the DHT content in the prostate was further reduced to undetectable values. In summary, the plasma levels of DHEAS, DHEA, delta 4-dione are markedly different between men and both animal models used and furthermore, measurements of prostatic levels of androgens suggest that the high plasma levels of these steroids are likely responsible for the presence of important amounts of DHT in human prostate after castration.     

Androgens and estrogens induce seasonal-like growth of song nuclei in the adult songbird brain

In seasonally breeding songbirds, the brain regions that control song behavior undergo dramatic structural changes at the onset of each annual breeding season. As spring approaches and days get longer, gonadal testosterone (T) secretion increases and triggers the growth of several song control nuclei. T can be converted to androgenic and estrogenic metabolites by enzymes expressed in the brain. This opens the possibility that the effects of T may be mediated via the androgen receptor, the estrogen receptor, or both. To test this hypothesis, we examined the effects of two bioactive T metabolites on song nucleus growth and song behavior in adult male white-crowned sparrows. Castrated sparrows with regressed song control nuclei were implanted with silastic capsules containing either crystalline T, 5alpha-dihydrotestosterone (DHT), estradiol (E(2)), or a combination of DHT+E(2). Control animals received empty implants. Song production was highly variable within treatment groups. Only one of seven birds treated with E(2) alone was observed singing, whereas a majority of birds with T or DHT sang. After 37 days of exposure to sex steroids, we measured the volumes of the forebrain song nucleus HVc, the robust nucleus of the archistriatum (RA), and a basal ganglia homolog (area X). All three steroid treatments increased the volumes of these three song nuclei when compared to blank-implanted controls. These data demonstrate that androgen and estrogen receptor binding are sufficient to trigger seasonal song nucleus growth. These data also suggest that T's effects on seasonal song nucleus growth may depend, in part, upon enzymatic conversion of T to bioactive metabolites.     

Androgens and estrogens induce seasonal‐like growth of song nuclei in the adult songbird brain

In seasonally breeding songbirds, the brain regions that control song behavior undergo dramatic structural changes at the onset of each annual breeding season. As spring approaches and days get longer, gonadal testosterone (T) secretion increases and triggers the growth of several song control nuclei. T can be converted to androgenic and estrogenic metabolites by enzymes expressed in the brain. This opens the possibility that the effects of T may be mediated via the androgen receptor, the estrogen receptor, or both. To test this hypothesis, we examined the effects of two bioactive T metabolites on song nucleus growth and song behavior in adult male white‐crowned sparrows. Castrated sparrows with regressed song control nuclei were implanted with silastic capsules containing either crystalline T, 5α‐dihydrotestosterone (DHT), estradiol (E₂), or a combination of DHT+E₂. Control animals received empty implants. Song production was highly variable within treatment groups. Only one of seven birds treated with E₂ alone was observed singing, whereas a majority of birds with T or DHT sang. After 37 days of exposure to sex steroids, we measured the volumes of the forebrain song nucleus HVc, the robust nucleus of the archistriatum (RA), and a basal ganglia homolog (area X). All three steroid treatments increased the volumes of these three song nuclei when compared to blank‐implanted controls. These data demonstrate that androgen and estrogen receptor binding are sufficient to trigger seasonal song nucleus growth. These data also suggest that T's effects on seasonal song nucleus growth may depend, in part, upon enzymatic conversion of T to bioactive metabolites. © 2003 Wiley Periodicals, Inc. J Neurobiol 57:130–140, 2003     

Physiological changes in androgen plasma levels with elapsing of time from castration in adult male rats

In the present study we investigated in adult male rats the effects of castration on Dehydroepiandrosterone (DHEA), Androstenedione (delta 4), Testosterone (T) and Dihydrotestosterone (DHT) plasma levels: five days (group II), seven weeks (group III) and eleven weeks (group IV) after orchiectomy. The same hormone assays were performed in rats approximately 60 days of age which underwent a sham-operation for orchiectomy (group I). Our data show that five days following orchiectomy (group II) delta 4, T and DHT were decreased with respect to sham-operated rats. (Group I: delta 4: 83.3 +/- 14.9 (SEM) ng/dl (n = 12); T: 435.32 +/- 51.45 (n = 12); DHT: 51.47 +/- 6.54 (n = 12); Group II: delta 4: 44.81 +/- 6.09 (n = 12) P = 0.05; T: 25.54 +/- 2.88 (n = 12) P less than 0.01; DHT: 12.9 +/- 2.51 (n = 12) P less than 0.01). Seven weeks afterwards T and DHT remained significantly lower (group III: T: 54.37 +/- 12.21, n = 16) (P less than 0.01; DHT: 33.22 +/- 4.49 (n = 16) P less than 0.01) while eleven weeks after all steroids were significantly decreased with respect to the values observed in sham-operated rats. (Group IV) delta 4: 32.01 +/- 5.7 (n = 10) P less than 0.01: T: 27.29 +/- 7.05 (n = 10) P less than 0.01; DHT: 29.03: 5.34 (n = 10) P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Self-administration of estrogen and dihydrotestosterone in male hamsters

Anabolic-androgenic steroids (AAS) are drugs of abuse. Previous studies have shown that male and female hamsters self-administer testosterone (T) and other AAS, suggesting that androgens are reinforcing in a context where athletic performance is irrelevant. AAS are synthetic derivatives of T, which may be aromatizable to estrogen and/or reducible to dihydrotestosterone (DHT). However, we do not know which metabolites of T are reinforcing. To determine if DHT, estradiol (E(2)), or DHT + E(2) are reinforcing, we tested intracerebroventricular (icv) self-administration in male hamsters. The hypothesis was that androgen reinforcement is sensitive to both androgenic and estrogenic T metabolites. If so, hamsters would self-administer DHT, E(2), and DHT + E(2). Twenty four castrated male hamsters (n = 8/group) received icv cannulas and sc T implants for physiologic androgen replacement. One week later, hamsters self-administered DHT (0.1, 1.0, 2.0 microg/microl), E(2) (0.001, 0.01, 0.02 microg/microl), or DHT + E(2), each for 8 days in increasing concentration (4 h/day). Operant chambers were equipped with an active and inactive nose-poke. At the medium concentration, hamsters self-administered DHT (active nose-poke: 47.9 +/- 13.9 responses/4 h vs. inactive: 18.7 +/- 4.8), E(2) (active: 44.8 +/- 14.9 vs. inactive: 16.6 +/- 2.6), and DHT + E(2) (active: 19.1 +/- 2.4 vs. inactive: 10.4 +/- 2.4, P < 0.05). At the highest concentration, males self-administered DHT (active: 28.3 +/- 7.7 vs. inactive: 15.0 +/- 3.5, P < 0.05) and DHT + E(2) (active: 22.6 +/- 3.8 vs. inactive: 11.6 +/- 2.5, P < 0.05), but not E(2). Hamsters did not self-administer the lowest concentrations of DHT, E(2), or DHT + E(2). These results support our hypothesis that both androgenic and estrogenic T metabolites are reinforcing. Together, they do not exert synergistic effects.     

Effect of nadolol on plasma lipids in hyperthyroidism

The effect of Nadolol treatment on lipid subfractions in a group of 23 hyperthyroid patients was assessed in a randomised double-blind placebo controlled trial lasting six weeks, carbimazole being given to both groups from weeks 2 to 6. Clinical and biochemical euthyroidism was seen in both groups at 6 weeks; no effect of nadolol on peripheral monodeiodination of T4 to T3 was observed. At time 0 there were significant negative correlations between total cholesterol and free T3 (r = 0.68), and free T4 (r = 0.54). In the Nadolol group there were significant rises between 0 and 6 weeks in total cholesterol (52.6%, P less than 0.01), LDL cholesterol (30.3%, P less than 0.01) and HDL cholesterol (18.2%, P less than 0.05). HDL cholesterol rose significantly in the placebo group (12.4%, P less than 0.05) but there were no significant increases in LDL cholesterol or total cholesterol. The rise in triglyceride during this period in the Nadolol group (64.7%, P less than 0.05) was significantly greater (P less than 0.05) than the rise in the placebo group (8.8%). Nadolol increases triglyceride more than placebo during the early management of hyperthyroidism.     

Differential maintenance of penile responses and copulatory behavior by gonadal hormones in castrated male rats

Sexually experienced male rats were castrated and immediately received implants of Silastic tubing containing either testosterone (T), dihydrotestosterone (DHT), estradiol (E), or nothing (blank). The ability of these hormone treatments to maintain precastration levels of copulatory behavior and ex copula penile responses was assessed for 40 days after castration. Throughout the study T- and E-treated males, but not males with DHT or blank implants, maintained normal copulatory behavior. In contrast males treated with T and DHT, but not E or blanks, maintained penile responses ex copula. In blank-treated males, penile-response latencies increased more rapidly than did intromission latencies. These results, together with those of previous studies, appear to rule out a role for estradiol and reinforce the role of androgens in the activation of rats' penile-response potential ex copula. Similarly, the results support the conclusion that in castrated male rats estradiol treatment is sufficient for the activation of masculine copulatory behavior, and that the penile actions necessary for intromission are not dependent on androgen. Thus, the evocability of penile actions and their relative androgen dependence are context sensitive.     

The effects of androgen and antiandrogen on dominance and aggressiveness in male red-winged blackbirds

Male red-winged blackbirds were given implants of testosterone or flutamide in order to manipulate the level of androgen reaching receptor sites. Implants of cholesterol were given as controls. Radioimmunoassay showed higher levels of testosterone and DHT in the plasma of testosterone-implanted birds than in the plasma of the pooled flutamide-implanted and cholesterol-implanted birds. Dominance was significantly correlated with effective androgen level. Androgen level was not correlated with rates of supplantations per subordinate but was correlated with rates of escalated attacks per subordinate. Thus androgen level influences dominance in male red-winged blackbirds by influencing one component of aggressiveness.     

Relationship between exercise-induced changes in serum and hepatic cholesterol metabolism in rats

The purpose of the present study was to determine the effects of exercise training on serum cholesterol level and hepatic cholesterol metabolism in rats. Twenty-four male Wistar strain rats, aged 6 weeks, were assigned to one of three experimental groups; control (n = 8), exercised 20 minutes a day (E20, n = 8), and exercised 60 minutes a day (E60, n = 8). Rats were sacrificed after ten weeks exercise. The levels of serum total cholesterol and HDL-cholesterol in the group E20 and group E60 were lower than that of control, 8% and 24% (p less than 0.01) for the total cholesterol and 10% and 24% (p less than 0.05) for the HDL-cholesterol, respectively. The activity of HMG-CoA reductase in liver microsome was significantly higher in the group E60 than that of control. The hepatic microsomal HMG-CoA reductase activity was negatively related to serum total (r = -0.62, p less than 0.01) and HDL (r = -0.58, p less than 0.01) cholesterol levels. From these results, we concluded that the enhancement of the cholesterol metabolism in the liver by exercise is a major course of the exercise-induced change in serum cholesterol of Wistar rats.     

Evidence for a granulosa cell site of dihydrostestosterone metabolism in the adult rat ovary

The ovarian enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) converts dihydrotestosterone (DHT) to 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol), a reduced androgen that does not bind to the granulosa cell androgen receptor. To determine the relative contribution of the granulosa cells to total ovarian 3 alpha-HSD activity, adult rats treated with either medroxyprogesterone acetate (MPA) or vehicle underwent ovarian microdissection. 3 alpha-Hydroxysteroid dehydrogenase is primarily located in excised follicles and corpora lutea, and is inhibited in the follicles but not corpora lutea by MPA (P less than 0.05). Elimination of healthy granulosa cells while maintaining healthy theca cells by irradiation of the exteriorized ovaries with 6000 rads resulted in a marked reduction in 3 alpha-HSD to 19% of control levels on a per-organ basis (P less than 0.01). The granulosa cell is the major ovarian site for 3 alpha-hydroxylation of ring A-reduced C19 steroids in the adult rat.     

Interrelationships between plasma insulin-like growth factor-I (IGF-I) concentrations and plasma sex hormone levels in the growing male guinea-pig.

The aim of the present study was to determine the influence of androgens on Insulin-like Growth Factor-I (IGF-I) release at puberty in male guinea-pigs. After the animals were orchiectomised (CX) or sham-operated (SO) at the end of weaning, plasma testosterone (T), dihydrotestosterone (DHT) and IGF-I levels were measured by RIA at the 4th (W4), 8th (W8) and 12th (W12) week after delivery. Body weight (BW) was recorded before sampling at each stage of the experiment. Body growth was maximal between W4 and W8 for both SO (+97%) and CX (+84%). However SO were heavier than CX at W8 and W12. In SO, a surge of plasma IGF-I levels was observed between W4 and W8, concomitantly to the increase of androgen levels (IGF-I: +86%, P less than 0.01; T: +190%, P less than 0.001; DHT: +18%; P less than 0.01). Significant correlations between IGF-I, T, DHT and BW were found only from W4 to W8 but not from W8 to W12. In CX, IGF-I levels were higher than in SO at W4 (+72%, P less than 0.01) and at W12 (+39%, P less than 0.01). A surge of IGF-I levels (+47%, P less than 0.01) was also observed but was delayed compared to SO (between W8 and W12 vs W4 and W8). BW and IGF-I levels were significantly correlated during this period. Because the surge of IGF-I levels may occur even in absence of gonads, these results give evidence that the increases in IGF-I and androgens at puberty were independent in guinea-pigs during this period.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs

Different pharmacological effects of Crocus sativus have been demonstrated on guinea pig tracheal chains in previous studies. In the present study, the prophylactic effect of the extract of C. sativus and its constituent, safranal on lung pathology and total and differential white blood cells (WBC) of sensitized guinea pigs was examined. Guinea pigs were sensitized with injection and inhalation of ovalbumin (OA). One group of sensitized guinea pigs were given drinking water alone (group S) and three groups were given drinking water containing three concentrations of safranal (S+SA1, S+SA2 and S+SA3 groups), three groups, drinking water containing three concentrations of extract (S+CS1, S+CS2 and S+CS3 groups) and one group drinking water containing one concentration of dexamethasone (S+D group) (n=6, for all groups). The lung pathology was evaluated in control, non treated and treated sensitized groups. Total and differential WBC counts of lung lavage were also examined. All pathological indices in group S showed significant increased compared to control group (p<0.05 for lung congestion and p<0.001 for other groups). Total WBC number (p<0.001), eosinophyl percentage (p<0.001) in lung lavage and serum histamine levels (p<0.01) were also increased in sensitized animals compared to those of controls. Treatment of S animals with dexamethasone, all concentrations of the extract and safranal significantly improved lung pathological changes, most types of WBC and serum histamine levels compared to group S (p<0.05-0.001). Treatment of S group with first concentration of safranal also decreased total WBC. Treatment with safranal was more effective in improvement of most pathological changes, total and differential WBC count as well as serum histamine level (p<0.05-0.001). These results showed a preventive effect of the extract of C. sativus and its constituent safranal on lung inflammation of sensitized guinea pigs. The results also showed that the effect of the plant is perhaps due to its constituent safranal.     

Estrogen implants in the lateral habenular nucleus do not stimulate the onset of maternal behavior in female rats

The natural onset of maternal behavior in the rat is hormonally mediated. Estrogen, progesterone, and prolactin administered to ovariectomized females in amounts and sequences that produce circulating levels similar to those found during pregnancy stimulate the onset of maternal behavior. In fact, maternal behavior can be stimulated by estrogen alone, administered either peripherally or by implant in the central nervous system. The lateral habenula (Lhb), which is a necessary component in the neural circuit that supports maternal behavior, contains a subset of neurons with estrogen receptors. The present study investigated whether estradiol implants directly in the Lhb are sufficient to stimulate maternal behavior. Female rats, hysterectomized and ovariectomized on day 16 of pregnancy, received estrogen implants in the Lhb or, as a positive control, in the medial preoptic area (MPOA). An additional control group received cholesterol implants in the Lhb. All females were tested for pup retrieval, nest building, crouching behavior, locomotor activity, and carrying behavior. Estradiol implants into the Lhb did not stimulate the onset of maternal behavior. Females with estrogen implants in the Lhb scored significantly lower in pup retrieval and crouching behavior compared to females with implants in the MPOA and were not significantly different from females with cholesterol implants in the Lhb. There were also no significant differences in overall activity or carrying behavior among the groups.     

Induction of male-typical aggression by androgens but not by estrogens in adult female mice

Ovariectomized adult CF-1 female mice were implanted with silastic capsules containing either testosterone (T), dihydrotestosterone (DHT), methyltrienolone (R1881), estradiol (E2), diethylstilbestrol (DES), or oil vehicle and were tested for aggressive behavior. The androgenic treatments (T, DHT, R1881) were highly effective in promoting male-like aggression while the estrogens (DES, E2) were completely ineffective. Subsequent receptor-binding studies confirmed assumptions about the specificity of DES, DHT, and R1881 binding to estrogen and androgen receptors in mouse hypothalamus.     

A comparison of the effect of inhaled diuretics on airway reflexes in humans and guinea pigs.

The effects of nebulized diuretics on citric acid-induced cough and airway obstruction in guinea pigs and capsaicin-induced cough and increase in airway resistance in humans have been studied. Half-maximum inhibition of cough in the guinea pig was produced by 1.3 mM furosemide and 0.25 mM hydrochlorothiazide. Cough was inhibited by 78 +/- 9% by 3 mM furosemide (P less than 0.05) and 89 +/- 11% by 3 mM hydrochlorothiazide (P less than 0.01). At the same time, airway obstruction was inhibited by 50 +/- 9% (P less than 0.001) and 42 +/- 15% (P less than 0.05), respectively. Nebulized furosemide (3 mM) was without effect on the airway obstruction produced by inhaled histamine or acetylcholine in the guinea pigs. Intravenously administered furosemide (270 nmol/kg) did not affect citric acid-induced responses. In humans, aerosolized furosemide (9 mM) and hydrochlorothiazide (3.4 mM) reduced the percent increase in respiratory resistance from 22.1 +/- 3.7 and 15.6 +/- 3.4 to 10.5 +/- 4.9 and 9.4 +/- 3.3%, respectively (P less than 0.05), but were without effect on cough due to capsaicin. Thus both furosemide and hydrochlorothiazide inhibited airway obstruction in the guinea pig and reduced the capsaicin-induced increase in airway resistance in humans. However, whereas coughing was inhibited in the guinea pig, neither drug affected cough in humans. This difference in the action of the loop diuretic and thiazide, which interact differently with Na(+)-K(+)-Cl-transport within the airway mucosa, on the cough and airflow obstruction in guinea pig and humans supports the view that different sensory limbs are involved in these reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural uptake and metabolism of testosterone and dihydrotestosterone in the guinea pig

Neural tissues from adult, castrated male guinea pigs were examined for their capability to concentrate and metabolize [1,2-³H]testosterone (T) and [1,2-³H]dihydrotestosterone (DHT), both in vitro and in vivo. In vitro uptake of DHT and T was greater in the hypothalamus and anterior pituitary than in the cerebral cortex. With DHT as the substrate, the 800×g particulate concentration of this compound was highest in the hypothalamus, although in this tissue, particulate concentration was less than that of the cytoplasm. In the cerebral cortex 5α-androstane-3,17-dione was the most abundant metabolite, whereas 5α-androstane-3,17-dione, 5α-androstane-3α,17β-diol, and 5α-androstane-3β,17β-diol were all present in equivalent amounts in the hypothalamus and pituitary. Incubation with T resulted in the formation of DHT, 4-androstane-3,17-dione, and a compound with the mobility of 5α-(or 5β-)androstane-3,17-7-dione. The radioactivity associated with DHT was the most prevalent in the pituitary (1.3%), and least prevalent in the cerebral cortex (0.6%), and in all cases cytoplasmic concentration of this compound exceeded the concentration in the particulate fraction. Recrystallization failed to confirm the presence of estradiol-17β. Although there were no apparent tissue differences in the uptake of DHT or T 1 hour after their injection, intracellular distribution varied. In all tissues examined, that percentage of total radioactivity attributable to DHT was greatest in the 800×g particulate preparations, particularly in the hypothalamus. Thus neural tissues in the guinea pig, as in other species, exhibit differential uptake and metabolism of androgen through which physiological and behavioral effects may be mediated.