Induction of male sexual behavior in the rat by 7 alpha-methyl-19- nortestosterone, an androgen that does not undergo 5 alpha-reduction (original) (raw)

Effects of Testosterone and 7α-Methyl-19-Nortestosterone (MENT) on Sexual and Aggressive Behaviors in Two Inbred Strains of Male Mice

Hormones and Behavior, 1996

whereas aggressive behaviors of the MENT-treated gen, 7a-methyl-19-nortestosterone (MENT), which is not groups were not different from those of the castrated 5a-reduced to dihydrotestosterone, were compared to control groups. These results suggest that MENT can those of testosterone in two inbred strains of male restore both male sexual behaviors and reproductive ormice, C57BL/6J and DBA/2J, in two experiments. In the gan weights as effectively as testosterone, at one-third first experiment, seminal vesicle (SV) weights, kidney of the testosterone dose, without stimulating male agweights, and circulating steroid levels were examined in gressive behaviors. ᭧ 1996 Academic Press, Inc. castrated mice treated with three doses of testosterone (3.125, 12.5, or 50 mg/day) or four doses of MENT (1, 4, 16, or 64 mg/day) for 2 weeks to determine the optimal replacement levels of the two androgens for behavioral 7a-Methyl-19-nortestosterone (MENT) is a synthetic studies. Both testosterone and MENT dose-dependently androgen that is not 5a-reduced to dihydrotestosterone increased the SV weights that were greatly reduced, in (Agarwal and Monder, 1988; Sundaram, Kumar, and both strains, by castration. MENT was more effective . The use of MENT in a combination with than testosterone in increasing SV weights, fully restormale contraceptive drugs appears to be more effective ing them to intact levels in both strains, at the dose of than testosterone . In castrated 4 mg/day. At the dose of 12.5 mg/day, testosterone rerats, the relative potency of MENT vs testosterone is stored the SV weights completely in C57BL/6J and up to much greater in restoring bulbocavernosus plus levator 80% in DBA/2J mice. DBA/2J mice were more sensitive ani muscle weights and suppressing postcastration inthan C57BL/6J mice to both androgens, as measured crease in serum gonadotropin levels than in restoring by kidney weights, although circulating levels of either steroid were very similar between the two strains of seminal vesicles or prostate gland weights (Kumar, Dimice. In the second experiment, we investigated the efdolkar, Monder, Bardin, and Sundaram, 1992). MENT, fects of testosterone (12.5 mg/day) and MENT (4 mg/day) therefore, is expected to support male sexual behaviors on sexual and aggressive behaviors. In each strain, without overstimulating prostate growth, where the ef-MENT-treated and testosterone-treated mice showed fects of testosterone can be undesirably amplified by similar numbers of mounts or intromissions. MENT was its conversion to dihydrotestosterone. A recent study equally effective as testosterone to fully (C57BL/6J) or in male rats has indeed shown that 10 mg/day of MENT partially (DBA/2J) restore sexual behaviors as well as the fully restored sexual behavior (percent of animals with SV weights to the intact levels. In contrast, MENTmounts and intromissions) in castrated male rats foltreated mice of both strains were much less aggressive lowing 1 week treatment although recovery of ejaculathan testosterone-treated mice. In both C57BL/6J and tions took a longer time (Morali, Lemus, Munguia, Ar-DBA/2J mice, testosterone fully restored aggression to the intact levels as measured by aggression latency, teaga, Perez-Palacios, Sundaram, Kumar, and Bardin, 1993). This dose of MENT is 1/20 of the effective dose of testosterone. The effects of MENT on other types of

Testosterone, androstenedione, and 5α-dihydrotestosterone on male sexual behavior and penile spines in the hamster

Physiology & Behavior, 2008

Testosterone, androstenedione, and 5α-dihydrotestosterone on male sexual behavior and penile spines in the hamster. PHYSIOL BEHAV XX (6) 000-000, 2007. -The expression of masculine sexual behavior (MSB) in male hamsters is optimally stimulated by aromatizable androgens like androstenedione (AD) and testosterone (T), while the non-aromatizable androgen, 5α-dihydrotestosterone (DHT), exerting potent androgenic peripheral effects, only in high doses maintains MSB after castration. No data exist on the ability of these androgens to restore long intromissions after castration. In this study, AD, T, and DHT were administered to four-week gonadectomized, sexually experienced male hamsters, for three weeks, in doses of 25 μg/day or up to 1000 μg/day to compare their potency in restoring MSB, penile size, and penile spines growth. Plasma levels of these steroids and the metabolites estrone and estradiol, were determined at the end of the treatment period. Gonadectomy completely suppressed MSB and induced a regression of penile spines. AD was more potent than T in restoring MSB, ejaculatory behavior being displayed by most castrated subjects with a lower dose of AD (50 μg/day) than of T (300 μg/day), and long intromissions being shown by all AD-treated castrated hamsters but only by 20% of T-treated ones, when doses of 1000 μg/day were given. DHT did not stimulate any copulatory response. The three androgens, even at the lowest dose, partially stimulated penis and penile epithelium growth, DHT showing the highest potency. Treatment of castrated hamsters with AD (50 μg/day), restored steroid levels to similar values as those of intact animals. These results show that AD and T restored MSB even with a partial stimulation of penile spines growth, AD being more potent than T. In contrast, DHT did not restore MSB in the hamster in spite of its peripheral androgenic potency.

Prolonged reinstatement of sexual behavior in castrated male rats with an ether of testosterone, SC-16148

Hormones and Behavior, 1970

Castrated rats given a single large injection of an ether of testoster one, SC-16148, copulated more frequently and for a longer period of time than rats administered an equivalent amount of testosterone propionate. Latency to first ejaculation following treatment was shortest in the testo sterone propionate treated animals. The maximal behavioral response to each steroid was similar in time to peak responses of androgen sensitive tissue as measured in a separate study. Saunders (1966) found that the substitution of a trimethylsilyl ether for the propionic acid moiety in testosterone propionate resulted in a peculiar ly long-acting androgenic compo und. He reported a maximum physiological response in the seminal vesicles, ventral prostate, and levator ani muscle of castrated rats 20-30 days after a single injection of the 17-trimethylsilyl ether of testosterone (SC-16148). The duration of the effect and the magnitude of the response were greater than those produced after administration of the same amount of testosterone propionate, which produced a maximum re sponse in 7-10 days. The purpose of this study was to determine whether SC-16148 also has a long-acting effect on the sexual response of castrated males to estrous females. METHODS Thirty male rats of the Long-Evans strain were used as experimental subjects; they were 70 days old at the beginning of the experiment. Stimulus females from the Long-Evans and Sprague-Dawley strains were brought into behavioral estrus by a single subcutaneous injection of 333 f.1g estradiol benzo ate in oil, 1 48-72 hours before testing. Each female received an injection

Prostate-Sparing Effects in Primates of the Potent Androgen 7α-Methyl-19-Nortestosterone: A Potential Alternative to Testosterone for Androgen Replacement and Male Contraception 1

The Journal of Clinical Endocrinology & Metabolism, 1998

7␣-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that cannot be converted to dihydrotestosterone. In this study we determined the relative androgenic, antigonadotropic, and anabolic potencies of testosterone vs. MENT in the nonhuman primate M. fascicularis. In castrated monkeys, dose-response relationships were generated for the effects of testosterone and MENT on gonadotropin levels, prostate growth, body weight, and lipid metabolism. In a pilot study, four monkeys were castrated, and magnetic resonance imaging (MRI) was used to document a 50% loss of prostate volume within 8 weeks, verifying that MRI is a reliable means to measure prostate size in this species. Two additional groups of six monkeys each were then castrated and serially administered four graded dosages of testos-terone or MENT via osmotic minipumps over 20 weeks. Complete suppression of LH was achieved with a minimum of 0.3 mg/day MENT, compared to 3.0 mg/day testosterone. MENT supported body weight 10 times more potently than did testosterone. Baseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3 mg/day testosterone. Thus, in monkeys, MENT is 10 times more potent than testosterone with regard to the clinically desirable end points of gonadotropin suppression and anabolism, but only twice as potent at stimulating prostate growth. These results suggest that MENT may have a wider therapeutic index than testosterone for human androgen replacement and male contraception. (J Clin Endocrinol Metab

Testosterone is required for the stimulatory effects of 8-OH-DPAT on sexual behavior in castrated male rats

European Journal of Pharmacology, 1993

The stimulatory effects of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) on male sexual behavior in the absence and presence of testosterone were investigated. Male rats (n = 12) were castrated and tested for sexual behavior (15 min, with an estrous female) up to 1 year after castration. Castration caused an abrupt decrease (50%) in the number of intromissions before first ejaculation, and the number remained stable for about 8 weeks. Between 8-12 weeks after castration, when ejaculation frequency was low, 0.2 or 0.4 mg/kg 8-OH-DPAT had no effect on ejaculation frequency, but significantly decreased the number of intromissions before first ejaculation. In weeks 17-18 after castration, 0.4 mg/kg 8-OH-DPAT no longer affected copulatory behavior. A 5-mm testosterone-filled Silastic capsule (implanted at week 19 after castration) resulted in subnormal plasma testosterone levels (mean 4.4 nmol/l) and did not fully restore male copulatory behavior. Administration of 8-OH-DPAT (0.2 and 0.4 mg/kg) was followed by an increase in ejaculation frequency and a decrease in ejaculation latency. Five months later, when plasma testosterone levels were very low (mean 0.6 nmol/l), 8-OH-DPAT (0.4 mg/kg) significantly increased the mean number of intromissions and ejaculations and decreased the number of intromissions before first ejaculation, intromission latency and ejaculation latency (borderline). The present results suggest that testosterone is required for the activating effects of 8-OH-DPAT on sexual behavior in castrated male rats, tested 17-52 weeks after castration. Sexual behaviour; Ejaculation; Castration; 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin); Testosterone; (Wistar rat)

Steroid regulation of sexual behavior

Journal of Steroid Biochemistry, 1976

Experimental data on rats and rabbits are reviewed, in support of the idea that estrogen is involved in the control both of male and female sexual behavior in these species. Female sexual behavior is stimulated by estrogen alone or estrogen in combination with progesterone. It can, however, also be induced by aromatizable, but not by non-aromatizable, androgens. Masculine sexual behavior is stimulated by aromatizable androgens or by non-aromatizable androgens combined with estrogen. The stimulatory effect of androgen on masculine sexual behavior is blocked by some aromatization blockers. This blocking effect can be reversed by estrogen. It is suggested that under normal conditions estrogens and androgens interact in producing sexual behavior.

A study of the prostate, androgens and sexual activity of male rats

Reproductive Biology and Endocrinology, 2007

The prostate is a sexual gland that produces important substances for the potency of sperm to fertilize eggs within the female reproductive tract, and is under complex endocrine control. Taking advantage of the peculiar behavioral pattern of copulating male rats, we developed experimental paradigms to determine the influence of sexual behavior on the level of serum testosterone, prostate androgen receptors, and mRNA for androgen receptors in male rats displaying up to four consecutive ejaculations.

Effects of 6- and 7-hydroxy metabolites of 3β,17β-dihydroxy-5α-androstane on gonadotrophin and prolactin secretion and on sex accessories weight of male rats

Journal of Steroid Biochemistry, 1983

It has recently been shown that 3p,li'/Gdihydroxy-5a-androstane (3/%diol), a known testosterone metabelite, may be further hydroxylated in position 6 and 7. Because of the possible involvement of 3&diol in the control of gonadotrophin secretion. this work was aimed at investigating the effects of 3/$,6a,l7#& trihydroxy-5oc-androstane (ba-triol), 3/$7a, I7B-trihydroxy-5a-androstane (7a-trio]), 3fi.6~. 17p-trihydroxy-Sa-androstane (6/I-triol) and 3B,7b,l7fi-trihydroxy-5a-androstane (7/?-triol) on the secretion of LH, FSH and prolactin in long term castrated male rats.

Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat

Journal of andrology

The testosterone dose-dependency of several mating and nonmating behaviors was examined in the male rat, chemically castrated with a GnRH antagonist analog. Graded doses of testosterone enanthate (TE) were given to male rats to reinstate behaviors abolished by GnRH antagonist treatment. GnRH antagonist treatment alone markedly lowered serum LH, FSH and T concentrations and ventral prostate and testis weights. Open field behaviors were not significantly affected by GnRH antagonist treatment or castration. Scent-marking behavior was markedly suppressed by both castration and GnRH antagonist and restored by the lowest dose of TE (0.05 mg). All measures of male sexual behavior were impaired by GnRH antagonist treatment and castration and restored by the lowest dose of TE (0.05 mg). The doses of TE required to restore normal ventral prostate weights and testis weights were higher than those required to maintain scent marking and mating behaviors. No direct behavioral effects of the GnRH ...