Mg Of Testosterone Propionate Research Articles

Serum estradiol, testosterone and dihydrotestosterone in male monkeys treated with testosterone propionate.

Serum estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) were measured in juvenile (pre-pubertal) male rhesus monkeys injected with either 8 mg or 80 mg of testosterone propionate (TP). After one week, the three steroids were elevated and remained essentially unchanged for the duration of the study. There was little difference in serum E2 or DHT when comparing the two groups of steroid-treated monkeys. In contrast, T levels were consistently greater in the animals given the high dosage of TP.

Pharmacological induction of ovulation in old and neonatally androgenized rats

Pharmacological manipulations previously reported to induce ovulation in aged female rats were administered to females sterilized by neonatal androgen. L-DOPA or iproniazid phosphate were found to induce ovulation in some females which had received 5 μg testosterone propionate (TP) at 5 days of age but not in females exposed to higher dosages of TP. A second experiment directly compared the effectiveness of progesterone as well as L-DOPA and iproniazid phosphate to induce ovulation in aged and androgenized females. While the effects are similar, it appears that the aged female is more responsive to these treatments than the young female exposed to 5 μg TP neonatally. It is concluded that age related changes in reproductive physiology might be accounted for by changes in the activity of brain monoamines or brain steroid receptor mechanisms or both. The neonatally androgenized female would appear to be a useful preparation for the study of age-related changes in reproductive function.

Effects of estradiol benzoate, estrone, and propionates of testosterone or dihydrotestosterone on sexual and related behaviors of ovariectomized rhesus monkeys

Ovariectomized adult rhesus monkeys were injected daily for 10 days with either 1 mg of dihydrotestosterone propionate (DHTP), 1 mg of testosterone propionate (TP), 10 μg of estradiol benzoate (EB), or 500 μg of estrone (El). On the 5th and 10th days of treatment, females received two 24-min behavioral tests with each of two adult males. All females received every hormonal treatment during the course of the study, with the order of treatments counterbalanced. Prior to the initiation of an hormonal treatment, each subject received two tests with no hormone treatment (NORX). Three behaviors related to female proceptivity were recorded. Treatment with DHTP had no influence on any aspect of proceptivity measured, in comparison to the NORX condition, whereas El or TP treatment augmented the frequencies of two of the proceptive behaviors and EB increased all three. The response of the male toward the female was influenced by the female's hormonal condition. Treatment with TP or DHTP did not increase the frequency of male contact or the mount rate in comparison to the NORX condition, whereas EB or El treatment did. In addition, DHTP was the only steroid which failed to increase the percentage of tests with intromission or ejaculation when compared to NORX. Female receptivity, as measured by acceptance or rejection of male contacts, was not different for the NORX-, TP-, EB-, or El-treated conditions. DHTP treatment, however, reduced female receptivity in comparison to all other conditions. Treatment with DHTP or TP resulted in an increase in the frequency of female yawning behavior, whereas neither estrogen treatment showed any effect on this behavior. The influences of TP on female proceptive and male sexual behavior were never duplicated or even approximated by treatment of females with the nonaromatizable DHTP. Nor was there any evidence that TP inhibited female receptivity below the level characteristic of NORX females, as was true for DHTP.

Inhibition of testosterone-induced sexual behavior in the castrated male rat by aromatase blockers

The effect of some aromatase inhibitors (aminoglutethimide, 1,4,6-androstatrien-3, 17-dione, and 4-hydroxy-androstenedione) on testosterone propionate (TP)-induced copulatory behavior was tested in sexually inexperienced castrated male rats. A single injection of 6 mg of TP induced mounting in 48% and ejaculatory pattern in 19% of the rats within 120 hr. Treatment with the aromatase inhibitors (injections every 12 hr for 108 hr) suppressed ejaculation in all but one rat and significantly reduced the number of rats mounting and intromitting. Concurrent administration of estradiol benzoate (EB, 1 or 3 μg every 12 hr) prevented the inhibitory effect of aromatase blockers. No inhibitory effect of the aromatization blockers was observed in rats in which sexual behavior was induced by dihydrotestosterone (1 mg/day) and EB (2.5 μg/day) for 20 days. The results support the concept that aromatization is an essential step for the induction of male sexual behavior by androgen in the rat.

Assay of perinatal testosterone and influence of anti-progesterone and theophylline on induction of sterility

Mean serum levels of testosterone (T) determined by radioimmunoassay were found to be reliably higher in male than female rats at 21 days of gestation and 6 hr and 3 days after birth. However, serum T concentrations in individual female samples were frequently equal to or greater than those found in male samples. Another study was performed to evaluate whether protection against androgen in females might be associated with mechanisms involving circulating progesterone and cellular adenosine 3′5′-cyclic monophosphate (cAMP). Female rats were injected on the day of birth with 1.0 μg testosterone propionate (TP) or sesame oil in combination with theophylline, antiserum to progesterone or saline. Females injected with TP lost vaginal cyclicity. The duration of time after puberty before reaching the sterility criterion was approximately 86% and 35% shorter for TP-groups receiving theophylline and antiprogesterone, respectively, than for those injected with saline. Thus, progesterone might provide some protection against the defeminizing effects of T and cAMP could be involved in hormone action during the perinatal period.

Effect of neonatal testosterone and oestradiol treatment on the development of the hypothalamo-hypophysial axis in the female rat

The hypothalamic LH-RH content and the concentrations of pituitary and plasma LH were measured at various ages in female rats treated daily with 10 micrograms testosterone propionate or 10 micrograms oestradiol-17beta from birth to Day 15. Persistent vaginal oestrus was induced in all the treated rats. Both hormones significantly reduced the hypothalamic LH-RH content and pituitary and plasma LH concentrations. Hypothalamic LH-RH increased after cessation of treatment but pituitary LH did not return to normal levels. Plasma LH levels were significantly lower than those in control rats. It is concluded that testosterone propionate and oestradiol-17beta (1) have a direct negative feed-back influence on the hypothalamus in the neonatal female rat; (2) alter the normal pattern of plasma and pituitary LH in developing female rats; (3) prevent the cyclic secretion of plasma LH after maturity; and (4) probably cause a chronic impairment in the release of LH-RH.

The effects of low dose diethylstilbestrol administration in neonatal female rats

Two groups of ten female rats were injected with 0.5 μg or 1.0 μg diethylstilbestrol (DES) on day 5 or days 5 and 6, respectively. Other groups were injected with 100 μg testosterone propionate (TP) on day 5 or day 6, respectively. One group was kept as uninjected controls. Body weights were the same for all groups even though the treated animals showed precocious vaginal opening. Animals treated on day 5 with TP showed a greater precocity than those treated on day 6. In another experiment, groups of ten rats were treated on day 3 with 30 μg TP, 5.0 μg estradiol benzoate (EB), 0.5 (DES) and sesame oil. All but the oil injected animals showed persistent vaginal estrus. DES and EB treated rats showed an increase in the percentage of persistent estrus with increasing age. The ability of very low doses of DES to sterilize female rats is consistent with observations of a specific estrogen binding protein which is present in the blood of newborn female rats and does not appear to bind non-estrogen steroids, and thus would not block masculinization by DES or TP.

Development and decline of running behavior in rats with delayed anovulation

Running activity in an activity wheel develops slowly at puberty, reaching a maximum which is held until 100 days of age when a decline sets in. The purpose of this study was to determine whether changes in ovarian status play a role in the decline of running. The time of onset and decline of running in the peak levels achieved were comparable in intact rats, in rats ovariectomized at weaning age and given estradiol benzoate replacement in Silastic capsules and in rats rendered precociously persistent estrus as a result of neonatal treatment with 10 μg testosterone propionate (at 5 days of age). It can be concluded that the development of persistent estrus in rats treated neonatally with androgen is not preceded or accompanied by disturbances in running activity, that the early low dose androgen exposure does not alter the sensitivity of running activity to estrogen stimulation, and that the decline in running seen after puberty cannot be attributed to changes in ovarian status.

Neonatal androgen levels and avoidance learning in prepubescent and adult male rats

Neonatal male rats were injected with 1.25 mg of testosterone propionate (TP) and compared with oil-injected controls on the acquisition of an active and passive avoidance response at 25 days of age. The TP treated animals acquired the active avoidance response significantly faster than controls, but no differences were found between groups tested on the step-down passive avoidance task. The active-avoidance paradigm was repeated at 70 days of age, with experimental and control animals receiving the same neonatal treatment as the prepubescent subjects. Again the TP group showed facilitated acquisition of the active avoidance response. The TP treatment also produced an increase in activity levels and aversion threshold to footshock in the prepubescent animals. Therefore the active avoidance effect may be interpreted more parsimoniously as a reflection of these latter effects, rather than learning per se.

Examination of some factors that control the effects of septal lesions on lordosis behavior

Various experimental parameters related to the effects of septal lesions on the lordosis behavior of rats have been examined. First, the failure of septal lesions to facilitate lordosis behavior in male rats appears to be related to the degree of exposure to androgens neonatally. The normal facilitation in lordosis behavior associated with septal destruction in adult female rats does not occur if these female rats are treated with 1.0 mg of testosterone propionate (TP) on Day 1 of life. Yet female rats given 270 μg of TP on Day 3 of life respond the same as do normal females to septal lesions. Second, these sexually dimorphic effects of septal lesions can be modified in adult rats by chronic treatment with gonadal hormones following septal destruction. Whereas previous studies indicated that chronic estrogen injections permit a facilitation in lordosis behavior to occur in septal lesioned male rats, the present results showed that chronic injections of TP following a septal lesion attenuates the facilitation in lordosis behavior typically observed in adult female rats following a septal lesion. Third, examination of the time course for the facilitation in lordosis behavior following a septal lesion revealed a four to six day delay before the appearance of heightened female sexual behavior. Fourth, in support of the possibility that modifications in lordosis behavior by septal lesions may be mediated by a depletion or imbalance in brain amines, amphetamine was found to reduce the high levels of lordosis behavior of septal lesioned female rats to control levels. Finally, further evidence of a potential role for brain amines in the effects of septal lesions was provided by the observation of significantly lower content and turnover of dopamine in the amygdala of septal lesioned female rats, relative to sham operated controls.

Progesterone treatment increases pituitary oestradiol retention in the ovariectomized normal female rat but not in the male nor in the androgen- or oestrogen-sterilized female rat.

Pituitary retention of [3H] oestradiol in ovariectomized rats was measured following in vivo progesterone pre-treatment and found to be significantly increased after 48, 72, 96 and 120 h of pre-treatment. Increased [3H]-oestradiol retention was also observed for at least up to 72 h after removal of the progesterone pre-treatment source. This retention was measured as DPM per mg dry tissue weight. [3H] Oestradiol retention was also measured in the nuclear fraction of tissues incubated with [3H]-oestradiol in vitro. Following 72 h of in vivo progesterone pre-treatment, the nuclear fraction from the pituitary was found to retain significantly more [3H]oestradiol than corresponding fractions from non-treated animals. In contrast to ovariectomized females, no increase in [3H]oestradiol retention was found in the pituitary of orchidectomized males pre-treated with progesterone for 72 h. [3H]Oestradiol retention by pituitaries of ovariectomized rats injected on the day of birth with 200 mug oestradiol benzoate (OeB) or 500 mug testosterone propionate (TP) was significantly decreased in comparison to control animals. When the rats were pre-treated in vivo with oestradiol for 6 or 72 h and [3H]oestradiol retention was measured 6 or 24 h after this pre-treatment, the OeB and TP treated animals retained significantly less [3H]oestradiol under most treatment conditions. Progesterone pre-treatment for 24 or 72 h in vivo followed by measurement of [3H]oestradiol retention immediately or 6 or 24 h later resulted in a significant increase in [3H]oestradiol retention for the control animals. In contrast, the neonatally OeB or TP treated animals differed significantly by not showing increased retention. When [3H]oestradiol retention of the pituitary was measured in vitro following homogenization at 0 degrees C and incubation at 37 degrees C for 1 h, the nuclear fraction from both OeB and TP treated animals was found to retain less hormone per unit DNA; however, this decrease was significant only for the TP animals. Thus, males and androgen- or oestrogen-sterilized females have an altered and reduced augmentation of pituitary oestradiol retention in response to both oestrogen and progesterone pre-treatments.

Effects of septal lesions on the courtship behavior of male ring doves ( Streptopelia risoria)

Male ring doves exhibit several androgen-dependent behavior patterns. Preliminary studies indicated that one of these, the nest-soliciting display, was selectively increased following septal lesions. In the present study castrated male ring doves received a septal lesion followed by daily intramuscular injections of 30 μg testosterone propionate (TP). Although one of the androgen-dependent displays, the bow-coo, was unaffected by the lesions, nest soliciting was significantly elevated during the period of hormone treatment. The restoration of nest-soliciting behavior in the males with septal lesions was even more rapid than that of unlesioned males receiving 200 μg TP/day, although after 12 days of treatment the performances of the latter came to approximate those of the males bearing septal lesions. Males that had received lesions in brain areas other than the septum were no more responsive to 30 μg of TP than were nonlesioned males receiving similar hormone treatment. It is suggested that the influence of the septum differs among the various androgen-dependent displays.

Responses in ovariectomized cows to repeated injections of thyrotrophin releasing hormone (TRH) and to oestradiol benzoate (ODB)

In the United States and Canada, there are no approved treatments for hypoactive sexual desire disorder in postmenopausal women. Testosterone improves female sexual desire in naturally- and surgically-menopausal women maintained on estrogen replacement therapy, and long-term safety data from randomized placebo-controlled clinical trials has yielded promising results. However, the mechanisms associated with its efficacy are not known, and could be addressed using preclinical rodent models; yet there is no systematic evaluation of the effects of estradiol and testosterone on female rat sexual behavior. The aim of these studies was to assess whether testosterone propionate (TP) facilitates sexual behaviors, particularly appetitive sexual behaviors, in Long-Evans and Wistar ovariectomized (OVX) rats primed with estradiol benzoate (EB). In Experiment 1, Long-Evans OVX rats were treated with Oil (O), 10 μg EB + O, O + 200 μg TP, 10 μg EB + 500 μg progesterone (P), or 10 μg EB + 200 μg TP. In Experiment 2a, Wistar OVX rats were treated with varying doses of EB (2.5, 5, or 10 μg) 48 h prior, and TP (0, 200, or 400 μg) 4 h prior to testing in a Latin-Square design. A subset of animals was used in Experiment 2b and treated sequentially with EB (0, 2.5, 5, or 10 μg) followed by TP (0, 200, or 400 μg, in a Latin-Square design) 48 h prior to sexual behavior testing. All tests occurred in the bilevel pacing chamber. Frequencies of female appetitive (hops/darts, solicitations, level changes) and consummatory (lordosis quotient and magnitude) sexual behaviors as well as the number of defensive behaviors towards males were scored. Number of mounts, intromissions and ejaculations from males were also scored. In EB-primed OVX Long-Evans rats, 200 μg TP administered 4 h prior to testing facilitated hops/darts and lordosis ratings beyond EB alone, and to levels equivalent to EB + P. In contrast, that regimen was not successful in EB-primed OVX Wistar rats. When EB and TP were co-administered 48 h prior to testing, 10 μg EB + 200 μg TP significantly increased hops/darts and level changes beyond that observed by 10 μg EB alone. In summary, the administration of EB and TP to OVX Long-Evans and Wistar rats facilitates appetitive measures of sexual behavior. Strain differences exist that likely reflect underlying differences in sensitivities to EB, and the EB-primed OVX Long-Evans rat may be useful for studying mechanisms of TP-facilitation of desire due to higher baseline sexual inhibition.

Postnatal thyroxine modifies effects of early androgen on lordosis

The sensitivity of female rats to the organizational effects of postnatal androgen was examined after néonatal manipulations known to affect the rate of brain development: thyroxine (T 4) administration and handling at birth. Testosterone propionate (TP) was injected subcutaneously in oil on postnatal day 6 to littermates that (i) had been undisturbed at birth; (ii) had received saline injections (S) and associated handling (H) on the day of birth (postnatal day 1) and the following day; and (iii) had received T 4 in saline (1 μg/g body wt) and H on postnatal days 1 and 2. Estrous cycles at 45 and 90 days of age, ovulation at Day 100 and sexual receptivity (lordosis score) at Days 115 and 125 were used to evaluate changes in TP effects. The majority of animals treated with 100 μg TP on postnatal day 6 exhibited persistent estrus (PE) at 45 and 90 days of age as expected. Neither T 4 nor S pretreatment on postnatal days 1 and 2 changed the incidence of PE. A reduction in ovarian weights and incidence of ovulation at 100 days of age supported cycle data in that only one out of 25 androgenized rats showed ovulation, compared with 16 of 22 controls. At approximately 115 days of age 2 μg of estradiol benzoate were administered for 3 days and 0.5 mg progesterone given on the 4th day 4 hr prior to placing females with sexually vigorous males. T 4-TP females exhibited higher (< .01) median lordosis scores than their S-TP littermates. The latter results were replicated in a second test conducted 10 days later ( p = .002). In addition, the second test indicated that the S-TP group had lower ( p = .005) lordosis scores than littermates given only TP neonatally. The results of these studies demonstrate that pretreatment with T 4 and handling, which are known, respectively, to hasten and retard the chronology of brain maturation, can exert differential effects on behavioral manifestations of postnatal TP without modifying androgen-induced sterility.

Aggression in male and female mice: Evidence for changed neural sensitivity in response to neonatal but not adult androgen exposure

Male mice were gonadectomized on Day 0, 2, 4, or 6 of life and were administered 300 μg testosterone propionate (TP) or oil daily beginning on Day 60. Over 90% of the TP-treated animals in each of the 4 groups exhibited aggressive behavior toward an olfactory bulbectomized male. Animals administered oil did not display fighting behavior. The day of gonadectomy, although not influencing the number of TP-treated animals that fought, did affect the time taken to display aggression in response to TP replacement. Mice gonadectomized on Day 0 required a longer exposure to TP than did animals gonadectomized on Day 2 in order to induce fighting. Similarly, mice gonadectomized on Day 2 required longer exposure to TP than did mice gonadectomized on either Day 4 or 6. There were no differences between mice gonadectomized on Day 4 and 6. In a second experiment, female mice, gonadectomized on Day 60, were given daily injections of either 500 μg TP or oil. Twenty-eight of 30 TP-treated mice fought whereas 2 of 30 Oil-treated mice fought. After a 60 day interval, the animals originally administered TP were re-administered the hormone and again tested for aggression. No differences were found between the amount of TP treatment required to initially induce aggressive behavior and the amount necessary to reestablish the behavior. Mice administered oil initially and then TP required the same amount of hormone treatment to induce aggression as did those animals given two TP treatments.

Effects of testosterone propionate treatment of neonatally ovariectomized rats on growth and subsequent responsiveness to oestrogen.

There was no significant difference in body weight between neonatally ovariectomized (OvX) rats whether given oil treatment or 90 mug testosterone propionate (TP) on day 3, when examined up to 23 weeks of age. When these two animals were injected with oestradiol benzoate (3 mug/day for 2 weeks), the neonatally OvX TP treated rats showed a significantly smaller depression in body weight than did the control neonatally OxX rats. Measurement of food intake also showed that TP treated rats responded significantly less to the depressant effects of oestrogen than did the controls. These data are consistent with the hypothesis that the ovary does restrain body weight in TP rats but that androgen treatment in the neonatal period may not have a specific effect on growth but may alter the sensitivity of growth regulating processes to the inhibitory effects of oestrogen.

FAMILIAL INCOMPLETE VIRILIZATION DUE TO PARTIAL END ORGAN INSENSITIVITY TO ANDROGENS

PEREZ-PALACIOS, GREGORIO; ORTIZ, SYLVIA; LOPEZ-AMOR, EZEQUIEL; MORATO, TOMAS; FEBRES, FREDDY; LISKER, RUBEN; SCAGLIA, HUGO Author Information

SERUM GONADOTROPHINS AND FOLLICULAR DEVELOPMENT IN IMMATURE RATS AFTER EARLY ANDROGEN ADMINISTRATION

Follicular development and serum gonadotrophin levels were studied in female rats after neonatal androgen administration. After injection of 1250 mug testosterone propionate (TP) on day 5 after birth the composition of the follicular population was altered: at nearly all ages the number of pre-antral follicles (follicular volume 2-20 X 10(5) mum2) was lower than in oil-treated rats, in some cases the number of small antral follicles (21-249 X 10(5) mum3) was also lower. Furthermore levels of serum follicle-stimulating hormone and luteinizing hormone were decreased from day 7 to day 20 suggesting that the high gonadotrophin levels before day 20 are of importance for normal follicular development. In contrast, final follicular maturation in TP-treated rats was enhanced; at day 35 more large antral follicles (follicular volume greater than or equal to 500 X 10(5) mum3) were present in TP-treated rats than in oil-treated rats. The presence of more large antral follicles was accompanied by higher plasma oestradiol concentrations, higher uterine weights and advanced vaginal opening. These results demonstrate an inhibition of normal follicular growth and an acceleration of ovarian maturation after neonatal androgen administration.

Androgenization: Alterations in Uterine Growth and Morphology1

Administration of exogenous androgen to neonatal female rats induces a syndrome of sterility characterized by anovulation and persistent vaginal cornification. As a step in the elucidation of the mechanisms by which neonatal hormone treatment alters the response of the adult to circulating steroid hormones, we have studied androgen induced alterations in uterine physiology and morphology. In females androgenized with a single injection of 1.25 mg of testosterone propionate on day 3, the uterus fails to respond to estradiol administration by growth but does atrophy following ovariectomy. Glycogen content is elevated. There is squamous metaplasia of the normally columnar luminal epithelium and a marked increase in and reorientation of stromal collagen. Our data suggest that the uterus of the androgenized female rat is tonically maximally stimulated and that androgenization also causes basic alterations in uterine morphology.

Lack of an effect of dihydrotestosterone on serum luteinizing hormone in neonatal female rats.

Department of Obstetrics and Gynecology, and Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02115, U.S.A. (Received 19 May 1975) Testosterone and its ring A reduced metabolite, dihydrotestosterone (DHT), lower gonadotrophin concentrations in weaned rats (Swerdloff, Walsh & Odell, 1972; Naftolin & Feder, 1973). While neonatally administered testosterone causes anovulatory sterility in adult female rats, similar treatment with DHT has no apparent effect upon central neuroendocrine programming (Brown-Grant, Munck, Naftolin & Sherwood, 1971; Whalen & Luttge, 1971), which raises the question of whether DHT can suppress gonadotrophins in the neonatal rat. In the first experiment, 5-day-old Sprague–Dawley-derived rats (Charles River Farms) were injected s.c. with 100 μg DHT propionate (DHTP), 100 μg testosterone propionate (TP, Eli Lilly & Co.) or the sesame oil diluent, and allowed to develop without further treatment. The injection volume was 25 μl. All animals were weaned on day 20. Daily vaginal