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Cohabitation with a female activates testosterone-dependent social aggression in male rats independently of changes in serum testosterone concentration.

Male hooded rats (350 to 450 g) were sham-castrated, castrated and implanted with testosterone-filled, or castrated and implanted with empty Silastic tubes. Twenty-four hours postoperatively the animals in each group were housed with a female or a male similar in size to the female. Beginning one week following surgery and continuing for three weeks thereafter, the female or male cagemate was removed once each week while a 15-min test of aggression toward an unfamiliar male intruder was conducted. During the aggression tests, lateral attacks, lunge attacks, bites, on-top, and piloerection were recorded. At the first aggression test, males housed with females were significantly more aggressive than their counterparts housed with males. In contrast, different testosterone regimes did not consistently influence the initial activation of intermale social aggression. At the second and third tests, males with testicular testosterone or a replacement were significantly more aggressive than their castrated controls on most measures but males housed with females continued to be more aggressive than the comparable group housed with males. These results suggest that normal fluctuations in serum testosterone concentration associated with sexual interaction are not necessary for the initial activation of intermale social aggression. Both repeated exposure to unfamiliar males as well as cohabitation with a female are effective stimuli for activation of testosterone-dependent social aggression.

Aggression↗

Measurement of the testosterone binding parameters for both testosterone-estradiol binding globulin and albumin in individual serum samples.

This report describes a solid phase method for the characterization of testosterone binding to both albumin and testosterone-estradiol binding globulin (TeBG). TeBG is adsorbed from serum samples onto a solid phase matrix of concanavalin A covalently linked to 4B Sepharose. The binding of testosterone is then examined both in the presence and absence of the endogenous serum albumin. Analysis of the resulting Scatchard plots permits determination of the TeBG binding capacity, TeBG association constant and a parameter of albumin binding equivalent to the product of its affinity and capacity for binding testosterone. Results showed that the TeBG capacity was lower in men than in women (18.4 +/- 5.8 vs. 33.1 +/- 19.2 nM, p less than 0.01). The association constant was greater in men (1.59 +/- 0.35 vs. 1.19 +/- 0.32 x 10(9)M-1, 10(9)M-1, p less than 0.01). There was no difference in the albumin binding parameter (43.8 +/- 18.3 vs. 46.6 +/- 15.5, NS). These parameters can then be used to calculate the distribution of the circulating testosterone into albumin bound, TeBG bound and unbound fractions.

Adult↗

Testosterone treatment in men with erectile disorder and low levels of total testosterone in serum.

Since decreased serum levels of testosterone (T) do not necessarily predict good outcome of testosterone treatment for erectile disorder, the purpose, of this study was to determine which men with erectile disorder and decreased serum levels might benefit from treatment. From a sample of 31 men (mean age = 39 years), 15 (48%) with erectile disorder and decreased serum levels of T responded well after 8 weeks of testosterone treatment (100 mg of testosterone propionate in the sustained-release form given im once a week). Good treatment outcome was associated with several variables, but only high levels of luteinizing hormone (LH) and low values of the T/LH (testosterone/LH) ratio consistently emerged as significant correlates and/or predictors of effective treatment. Levels of LH above 7.5 IU/L or the values of the T/LH ratio equal to or below 0.87 nmol/IU in patients with erectile disorder and decreased serum levels of T suggest that testosterone treatment may be effective.

Adult↗

Testosterone as a social inhibitor: two case studies of the effect of testosterone treatment on language.

This study aimed to correlate testosterone levels with natural written language in 2 people undergoing testosterone therapy. Two participants, a man receiving treatment for loss of upper-body strength and a female-to-male transgendered individual, supplied records of injections over 1-2 years along with e-mails or journal entries as writing samples. Results showed that higher testosterone levels correlated with reduced use of words related to social connections. Language relating to anger, sexuality, and achievement was unrelated to testosterone levels. It appears that testosterone steers attention away from social connections but not necessarily toward concerns with aggression or sexual activity.

Adult↗

Plasma testosterone and testosterone binding affinities in men with impotence, oligospermia, azoospermia, and hypogonadism.

Mean plasma testosterone levels (+/- S.D.), using Sephadex LH-20 and competitive protein binding, were 629 +/- 160 ng/100 ml for a group of 27 normal adult men, 650 +/- 205 ng/100 ml for 27 impotent men with normal secondary sex characteristics, 644 +/- 178 ng/100 ml for 20 men with oligospermia, and 563 +/- 125 ng/100 ml for 16 azoospermic men. None of these values differ significantly. For 21 men with clinical evidence of hypogonadism the mean plasma testosterone (+/- S.D.), at 177 +/- 122 ng/100 ml, differed significantly (P < 0.001) from that of the normal men.The mean testosterone binding affinities (as measured by the reciprocal of the quantity of plasma needed to bind 50% of (3)H-testosterone tracer) were similar for normal, impotent, and oligospermic men. Though lower for azoospermic men the difference was not significant (P >0.1). For 12 of the 16 hypogonadal males the testosterone binding affinity was normal, but raised binding affinities, similar to those found in normal adult females or prepubertal boys (about twice normal adult male levels), were found in four cases of delayed puberty. These findings help to explain why androgen therapy is usually useless in the treatment of impotence.

Adult↗

Cortisol, testosterone, and free testosterone in athletes performing a marathon at 4,000 m altitude.

Cortisol, testosterone, free testosterone and the ratio between free testosterone and cortisol (FTCR) were monitored in six athletes participating in a marathon starting at 3,860 and finishing at 3,400 m, having reached the top at 5,100 m altitude. Blood was drawn at sea level before the departure for the mountain area, after a week of acclimatization, immediately after the marathon and after a 24-hour recovery period from the run. Cortisol increased after acclimatization and especially after the marathon; it decreased to normal values after recovery. Testosterone decreased after acclimatization, especially after the run; it presented a partial recovery 24 h after the race. Free testosterone did not decrease after acclimatization and presented partial recovery. FTCR could also be useful for monitoring fitness, overtraining and overstrain in strenuous and ultraendurance exercise.

Adult↗

Does prolactin modify testosterone feedback in the hamster? Pituitary grafts alter the ability of testosterone to suppress luteinizing hormone and follicle-stimulating hormone release in castrated male hamsters.

Adult male golden hamsters maintained in a long photoperiod (14 h of light and 10 h of darkness) or in a short photoperiod (5 h of light and 19 h of darkness for 7 weeks) were castrated and either given one anterior pituitary transplant under the kidney capsule or sham-operated. Additional animals were castrated and grafted or sham-grafted at the time of transfer to the short photoperiod. Starting 2 weeks after castration, all animals were injected three times a week with 20 micrograms testosterone propionate (TP). After 3 weeks, the dose of TP was increased to 80 micrograms and, after an additional 2 weeks, to 320 micrograms per injection. Blood samples were collected 2 weeks after castration and 1 day after the last injection of 20, 80, and 320 micrograms TP. Short photoperiod reduced and pituitary grafts increased plasma PRL levels. Plasma testosterone levels were related to the dose of injected TP, but were not influenced by photoperiod or pituitary transplants. Before the onset of TP injections, plasma LH and FSH levels in grafted and sham-grafted hamsters did not differ. In each of the three photoperiod conditions, injections of TP were consistently less effective in suppressing plasma gonadotropin levels in pituitary-grafted animals than in sham-grafted controls. These results indicate that PRL modulates the effects of exogenous testosterone on LH and FSH release in adult castrated male golden hamsters, this effect of PRL is due to reducing the sensitivity of the hypothalamic-pituitary system to feedback inhibition by testosterone, and suppression of pituitary PRL release in short photoperiod may be partially responsible for the concomitant increase in the sensitivity of LH and FSH release to inhibition by testosterone.

Animals↗

A comparison of the effects of neonatally administered testosterone, testosterone propionate and dihydrotestosterone on aggressive and sexual behaviour in the female golden hamster.

Female golden hamsters received one of the following treatments on the day following birth: (i) 300 mug testosterone propionate in arachis oil, (ii) 300 mug testosterone in oil, (iii) 300 mug dihydrotestosterone in oil, or (iv) oil alone. As adults all animals, underwent three tests for behaviour. First, while intact, females were observed in aggressive interactions with males. Secondly, after ovariectomy, females were primed with oestrogen + progesterone and tested for receptivity with a stud male. Thirdly, all ovariectomized females were primed with testosterone propionate and tested for male patterns of behaviour with a receptive female. Compared with the effects of oil administration (control), testosterone propionate administration resulted in increased aggressiveness and the capacity to show male patterns of sexual behaviour, together with a decreased capacity to show female patterns of sexual behaviour. Testosterone increased aggression and male sexual behaviour, but had no effects on receptivity, while dihydrotestosterone decreased some components of receptivity but had no effects on aggressiveness or the capacity to show male mating behaviour.

Aggression↗

Effects of testosterone, testosterone metabolites and anti-androgens on the function of the male accessory glands in the rabbit and rat.

The androgenic potencies of testosterone, 5alpha-dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol and 5alpha-androstane-3beta,17beta-diol towards the prostate, glandula seminalis+glandula vesicularis, ampullae and epididymis were evaluated after administration to castrated rabbits. The influence of cyproterone acetate, stilboestrol and medrogestone on accessory gland function was also investigated in rabbits and rats. In the rabbit it was found that the minimum dose of testosterone propionate that would maintain the function of all accessroy glands at normal levels was approximately 200 microgram/animal/day. Higher levels of testosterone propionate overstimulated the function of the prostate, glandula seminalis+glandula vesicularis and ampullae, but did not affect the epidiymis. Whereas testosterone propionate and 5alpha-dihydrotestosterone propionate were essentially equipotent in their capcity to support growth and secretory activity and stimulated all the accessory glands, 5alpha-androstane-3alpha,17beta-diol dipropionate had a pronounced differential effect; it was considerably more potent than testosterone propionate in promoting secretion in the prostate, but was ineffective in maintaining the function of the epididymis. 5alpha-Androstane-3beta,17beta-diol dipropionate was the weakest androgen tested. Evidence also indicated that the potency of a steroid can depend on whether it is administered as its free or esterified form. Cyproterone acetate suppressed fructose secretion in the prostate of the rabbit but had no adverse effects on the function of the epididymis in either the rabbit or rat. Stilboestrol was the most potent anti-androgen tested and medrogestone the least effective.

Androgen Antagonists↗

Effects of FSH and testosterone on highly purified rat Sertoli cells: inhibin alpha-subunit mRNA expression and inhibin secretion are enhanced by FSH but not by testosterone.

The effects of FSH and testosterone on inhibin mRNA expression and inhibin production by highly purified Sertoli cell preparations were examined. Sertoli cells were isolated from testes of 22-day-old rats by sequential trypsin, collagenase and hyaluronidase treatments, with subsequent osmotic shock treatment on day 3 of culture. Contamination by peritubular and germ cells was less than 0.5 and 1-3% respectively. Intracellular and secreted inhibin levels were measured by radioimmunoassay, using Sertoli cells which were incubated for 24 h in the absence or presence of FSH and testosterone from days 4 to 5 of culture. FSH stimulated the cellular inhibin content and the secreted inhibin level by four- and sevenfold respectively, with a half-maximal effective dose of 5-50 ng/ml. Under the present incubation conditions, testosterone (1 mumol/l) had no effect on immunoreactive inhibin levels in either the presence or absence of FSH. Similarly, the expression of inhibin alpha-subunit mRNA was increased following FSH stimulation, whereas testosterone had no effect. The expression of inhibin beta B-subunit mRNAs was not influenced by FSH or testosterone. It is concluded that highly purified Sertoli cell preparations, with a very low number of peritubular or germ cells, are fully responsive to FSH with respect to inhibin mRNA expression and inhibin production.

Animals↗

Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system.

PURPOSE: The effects of androgen replacement via a nonscrotal permeation enhanced testosterone transdermal system on the sexual function of men with hypogonadism were assessed. MATERIALS AND METHODS: An open label, multicenter study of testosterone supplementation and withdrawal was conducted with sexual function assessed by the Watts and Davidson questionnaires and RigiScan monitoring. RESULTS: When comparing results obtained during use of the testosterone transdermal system (with normalized testosterone levels) and during the androgen withdrawal period, nocturnal erections occurred more frequently with longer duration and greater rigidity, and patient assessments of sexual desire and weekly number of erections were higher. CONCLUSIONS: Sexual function improved significantly in men with hypogonadism treated with the testosterone transdermal system.

Administration, Cutaneous↗

7 alpha-Biotinylated testosterone derivatives as tracers for a competitive chemiluminescence immunoassay of testosterone in serum.

Ring core-biotinylated testosterone tracers were synthesized with bridges of three different lengths connecting the biotin moiety to the steroid core (7 alpha-Cn-Bio-T, n = 3, 6, or 11). Together with a position 7-specific polyclonal anti-testosterone antibody, we used the 7 alpha-C11-Bio-T tracer to develop a novel, labeled-hapten competitive immunoassay for total testosterone in serum. (The C3 and C6 tracers proved to be not suitable for analogous immunoassays.) Enhanced chemiluminescence signal was generated by use of a second immobilized antibody and a streptavidin-horseradish peroxidase conjugate. The measuring range of the assay is 0.2-20.0 nmol/L, linearity of serial dilutions can be demonstrated, the lower detection limit is 0.125 nmol/L, and the interassay imprecisions are 13-16%. Accuracy determinations in mass spectrometry-controlled reference specimens showed a mean recovery of 95%. In addition, the assay shows low cross-reactivities, demonstrating the favorable specificity of the combination of a "nearly native" tracer with a position analog antibody. The optimized steric structure and the long spacer arm of the biotinylated testosterone tracer make this chemiluminescence assay well-suited for measuring total testosterone concentration in serum.

Adolescent↗

Extended Hildebrand solubility approach: testosterone and testosterone propionate in binary solvents.

Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log alpha 2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.

Chemistry, Pharmaceutical↗

Effect of actinomycin D or puromycin on microsomal testosterone hydroxylase activity enhanced by testosterone in female rat liver.

The injection of testosterone propionate for 4 successive days into female rats resulted in an increase of the in vitro conversion of the hydroxylated testosterones from testosterone by the hepatic microsomal fraction, but no change in the content of microsomal cytochrome P-450 occurred. Actinomycin D or puromycin, which was administered for 4 days with injections of testosterone propionate, prevented the enzyme induction.

Animals↗

Plasma testosterone levels and ovarian testosterone content in adult mice treated with diethylstilbestrol neonatally.

Neonatal female NMRI mice (n = 16) were treated with 5 micrograms diethylstilbestrol (DES) per day, for the first 5 days after birth and killed postpubertally. Control females (n = 52) were injected with vehicle only and killed in different stages of the estrous cycle. The plasma testosterone level was significantly lower in DES females than in control females in any of the estrous phases. Ovariectomy (n = 5), adrenalectomy (n = 5) or a combination of both ablations (n = 3) did not affect the plasma testosterone in DES treated females while it was significantly reduced in control females (ovariectomy n = 5; adrenalectomy n = 9); most effective was the combination ovariectomy-adrenalectomy (n = 7). Ovarian homogenates from DES treated females (n = 10) had a significantly lower testosterone content than homogenates from control females in any phase of the estrous cycle (6-10 females per phase), which held true on both a per ovary basis and when related to ovarian weight. After a 2 h incubation in vitro, the testosterone levels had increased significantly in DES homogenates (n = 6) and to a lower extent in homogenates from control females in estrus (n = 9). No similar effect was found in homogenates from diestrus (n = 10) or proestrus (n = 9) females. The results are discussed in relation to the special ovarian morphology of adult but neonatally DES treated females and also with respect to endocrine control mechanisms.

Adrenalectomy↗

Testicular testosterone concentration and in vitro response to HCG in normal and in testosterone immunized rabbits.

The testosterone concentration, the in vitro response to HCG and the percentage Leydig cells in testes of normal and of testosterone-3-BSA immunized rabbits were determined. Following immunization all three parameters increased in the same order of magnitude (1.8-2.6fold). The results indicate that active immunization with testosterone has no deleterious effects on the endocrine capacity of the Leydig cells. The observed functional and morpholigical alterations of the testes are due solely to increased trophic hormone secretion from the pituitary caused by antibody binding of circulating androgens. The basic testosterone concentration in the testes of the control rabbits were in the range of values reported for other species.

Animals↗

The use of 6alpha-and 6beta-carboxymethyl testosterone-bovine serum albumin conjugates in radioimmunoassay for testosterone.

The synthesis of 6alpha- and 6beta-testosterone-bovine serum albumin (BSA) conjugates is described. 6beta-Carboxymethyl-4-androstene-3,17-dione was prepared by a route analogous to that described earlier for 6beta-carboxymethyl progesterone. Sodium borohydride reduction of the 3 and 17 keto groups and subsequent selective oxidation of the resulting 3beta, 17beta-diol using MnO2 provided 6 -carboxymethyl testosterone. Further acid catalyzed epimerization of the C-6 center gave the isomeric 6alpha-carboxymethyl testosterone. The 6alpha- and 6beta-testosterone derivatives were attached to BSA via a mixed anhydride coupling employing tributylamine and i minus-butylchlorocarbonate. For each molecule of BSA, the 6alpha- and 6beta-conjugates contained an average of 23 and 20 steroid residues, respectively. Antisera to the conjugates exhibited similar high specificities toward various steroids, the only incidence of serious cross-reaction being the expected case of dihydrotestosterone.

Androstenedione↗