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Effect of castration and testosterone propionate on mouse vibrissae.

Vibrissae of normal mice were measured for six cycles starting at birth. Groups of immature male albino mice were castrated at 21 days of age when E, F, G and H (Danforth nomenclature, 1925) vibrissae were in their first cycle of growth. Levels of testosterone in their peripheral plasma were reduced to about one tenth of the normal. The final length achieved by their vibrissae in all subsequent cycles was shorter than that of normal mice. Another group of immature male mice were treated with implants of testosterone propionate to give plasma levels of approximately five to ten times normal. Their vibrissae showed a significant increase in final length in all growth cycles before and after sexual maturation. Vibrissae of adult male mice treated with excess testosterone showed a significant increase in final length at the end of the growth cycle immediately after commencement of treatment. On the other hand, vibrissae of castrated adult mice showed a significant decrease in final length in the second successive cycle after castration. The rate of growth of all vibrissae remained unchanged. Changes in their final length were brought about by changes in the period of growth. Castrated mice had a slightly longer resting period.

Animals↗

Effects of active immunization against gonadotropin releasing hormone on gonadotropin secretion after ovariectomy and testosterone propionate administration to mares.

Five lighthorse mares were actively immunized against gonadotropin releasing hormone (GnRH) conjugated to bovine serum albumin (BSA) to study the involvement of GnRH in luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion following ovariectomy (OVX) and after administration of testosterone propionate (TP). Five mares immunized against BSA served as controls. Immunizations were started on November 1, and OVX was performed in June (d 1). All mares were treated with TP from d 50 to 59 after OVX. On the day of OVX, concentrations of LH were lower (P less than .05) in GnRH-immunized mares than in BSA-immunized mares and were generally nondetectable; FSH concentrations were reduced (P less than .05) by 50% in GnRH-immunized mares relative to BSA-immunized mares. In contrast to BSA-immunized mares, plasma concentrations of LH or FSH did not increase after OVX in GnRH-immunized mares. The LH response to GnRH analog (less than .1% cross-reactive with GnRH antibodies) on d 50 was reduced (P less than .05) by 97% in GnRH-immunized mares relative to BSA-immunized mares, whereas the FSH response was similar for both groups. Treatment with TP for 10 d reduced (P less than .01) the LH response and increased (P less than .01) the FSH response to GnRH analog in BSA-immunized mares, but it had no effect (P greater than .1) on the response of either gonadotropin in GnRH-immunized mares.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of implanting bull calves with testosterone propionate, dihydrotestosterone propionate or oestradiol-17 beta prepubertally on the pituitary-testicular axis and on postpubertal social and sexual behaviour.

Twelve non-implanted crossbred bull calves served as controls and 30 crossbred bull calves (10/treatment) were implanted for 82 days, beginning at 34 days of age, to determine the influence of testosterone propionate (TP), dihydrotestosterone propionate (DHTP) and oestradiol-17 beta (E2) on prepubertal and pubertal pituitary-testicular function and on postpubertal social and sexual behaviour. Compared with control bulls, concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin concentrations were suppressed (P less than 0.01) in all implanted bulls. Testosterone (T) concentration increased (P less than 0.001) in TP-implanted, but decreased (P less than 0.01) in DHTP and E2 bulls during the implant period. LH response to gonadotrophin-releasing hormone (GnRH) challenge during the implant period (2.5 months of age) was less (P less than 0.01) in TP, E2 and DHTP bulls than in controls. A small but significant T response to GnRH occurred in control bulls at 2.5 months of age. LH and T responses to GnRH challenge at 7 months of age (100 days after implant removal) was similar (P greater than 0.20) in control and implanted bulls. Steroid implants administered prepubertally had no effect (P greater than 0.10) on postpubertal social and sexual behaviours, including number of flehmen responses, abortive mounts, services and competitive order score. Body weight did not differ (P greater than 0.10) between treatment groups, but testis size was reduced (P less than 0.01) during the implant period and up to 10 months of age in treated bulls compared with controls. Testes remained smaller in E2-treated bulls up to the end of the study (23 months of age), but daily sperm production and epididymal weight did not differ (P greater than 0.10) between treatment groups at slaughter. Control bulls reached puberty earlier (P less than 0.01; 270 +/- 11 days of age) than did TP (302 +/- 11 days), DHTP (309 +/- 11 days) or E2 (327 +/- 11 days) bulls. Although puberty was delayed in all implant groups, there was no difference in scrotal circumference at puberty (average 28.4 +/- 0.4 cm) between treatment groups. Our findings indicate that TP, DHTP and E2 implants administered prepubertally result in acute suppression of serum LH, FSH and inhibin during the implant period and in post-implant suppression of testis size and delayed puberty in bulls. The lack of treatment effect on behaviour suggests that steroidal programming of sexual behaviour occurs before 1 month of age in bulls.

Animals↗

Masculinization of the female rat spinal cord following a single neonatal injection of testosterone propionate but not estradiol benzoate.

We previously reported that a motor nucleus of the rat spinal cord, the spinal nucleus of the bulbocavernosus (SNB), has more and larger neurons in males than females. The SNB is significantly masculinized in adult female rats receiving 1 mg of testosterone propionate (TP) on the second day of life, compared to that of their oil treated sisters. This masculinization consists of more neurons in the region of the SNB. These results are consistent with the hypothesis that the action of androgens during the early perinatal period is responsible for the sexually dimorphic development of the SNB. Neonatal TP caused no detected masculinization, i.e. enlargement of the size of individual neurons in this region in females. Male rats given TP on day 2 had significantly smaller testes and smaller SNB somas in adulthood than oil treated males. In female rats given 100 micrograms of estradiol benzoate (EB) on day 2, the SNB was not masculinized in either number of size when observed in adulthood. The lack of a masculinizing effect of EB suggests that the aromatization of testosterone to estradiol is not sufficient for this dimorphic development.

Animals↗

Effects of in vivo administration of testosterone propionate on in vitro production of follicle-stimulating hormone and luteinizing hormone by pituitaries of pony mares.

The in vitro incorporation of [3H]leucine into immunoprecipitable follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was assessed for pituitaries from pony mares treated with testosterone propionate (TP) or oil (controls). Mares were treated every other day with TP (n = 4) at 350 micrograms/kg of body weight or with an equivalent volume of oil (n = 4). One day following the sixth injection of TP, each mare received an intravenous injection of gonadotropin releasing hormone (GnRH) at 1.0 micrograms/kg body weight and was bled frequently for 4 h. Treatment of mares with TP reduced FSH (P less than 0.05) and LH (P less than 0.01) concentrations in daily blood samples and increased (P less than 0.01) the amount of FSH secreted in response to GnRH compared with control mares. Incorporation of [3H]leucine into immunoprecipitable FSH was also greater (P less than 0.01) in pituitaries from TP-treated mares compared with control mares on both a per mg tissue and per anterior pituitary basis. The amount of LH secreted after GnRH, the amount left in the pituitary and the incorporation of [3H]leucine into LH were not affected by treatment. These results confirm earlier conclusions drawn from indirect evidence that androgens increase the production of FSH in the mare.

Animals↗

Comparative effects of testosterone propionate, oestradiol benzoate, ICI 182,780, tamoxifen and raloxifene on hypothalamic differentiation in the female rat.

Hypothalamic differentiation in the female rat during the neonatal period is critically dependent on the steroid milieu, as permanent changes in reproductive function are observed after administration of oestradiol and testosterone during such a critical stage. Selective oestrogen modulators (SERMs) constitute a family of drugs that, depending on the tissue, are able to exert oestrogenic or antioestrogenic actions. The present experiments were conducted to analyse whether the SERMs, tamoxifen and raloxifene, can cause oestrogenic actions during the hypothalamic differentiation period. Postnatal female rats were injected between days 1 and 5 with 100 microg/day tamoxifen, raloxifene or ICI 182,780 (a pure antioestrogen). Other groups of animals were injected on day 1 of age with 100 microg oestradiol benzoate (OeB) or 1.25 mg testosterone propionate (TP) alone or in combination with raloxifene (500 microg/day between days 1 and 5). In all experimental groups, the age, body weight and concentrations of serum gonadotrophins at vaginal opening were recorded, whereas vaginal cyclicity and the negative and positive feedback between oestradiol and LH were monitored in adulthood. The results obtained confirmed the ability of high doses of OeB or TP to alter the normal differentiation of the brain permanently. They also reinforced the hypothesis that oestrogens are also necessary for normal brain differentiation in female rats because administration of a pure antioestrogen, such as ICI 182,780 permanently altered the function of the reproductive axis. In addition, our data provided evidence for different actions of the two SERMs under analysis (raloxifene and tamoxifen) upon peripheral targets, as raloxifene advanced vaginal opening whereas tamoxifen did not. In contrast, their actions on brain differentiation appeared similar and analogous to those obtained after neonatal administration of oestradiol, as evidenced by vaginal acyclicity, ovarian atrophy, sterility and abolition of negative and positive feedback between oestradiol and LH, thus suggesting an oestrogenic action of these SERMs on hypothalamic differentiation. Moreover, the oestrogenic activity of raloxifene was supported by its inability to block the effects of OeB and TP administered neonatally. In conclusion, the present results indicated that the SERMs, tamoxifen and raloxifene, exert an oestrogen-like effect upon hypothalamic differentiation of the neonatal female rat.

Analysis of Variance↗

Duration dependent induction of invasive prostatic carcinomas with pharmacological dose of testosterone propionate in rats pretreated with 3,2'-dimethyl-4-aminobiphenyl and development of androgen-independent carcinomas after castration.

Male F344 rats were first treated with 3,2'-dimethyl-4-aminobiphenyl for 20 weeks in the presence of testicular androgens and then administered of a pharmacological dose of testosterone propionate (TP) for various periods (maximum 40 weeks). This resulted in development of invasive carcinomas in the dorso-lateral prostate as well as the seminal vesicles whose incidences were TP duration-dependent. However, in situ carcinomas of the ventral prostate were not affected by the TP treatment and atypical hyperplasias were clearly decreased. When animals were subjected to orchiectomy after 20-weeks-treatment with the TP, invasive adenocarcinomas were still subsequently noted in the dorso-lateral prostate and seminal vesicles, demonstrating a certain androgen-independence. The data indicate that, in spite of the necessity of high dose of TP for induction of invasive prostate carcinomas in the present experimental model, a proportion of the resulting tumors are hormone-independent.

Aminobiphenyl Compounds↗

[Effect of testosterone propionate on the induction by 1,2-dimethylhydrazine of angiosarcomas of the renal capsule in castrated mice].

Administration of 1,2-dimethylhydrazine (DMH) produced 83% (15/18) of renal capsule angiosarcomas in CBA mice. Castration that preceded the DMH-treatment reduced tumor incidence to 7% (2/29). Simultaneous administration of DMH and testosterone propionate (TP) to castrated males restored the tumor frequency (100%, 24/24). Castrated males that received TP after the cessation of the DMH treatment developed tumors in 10% (3/31). Combined treatment of castrated females with DMH and TP resulted in the development of angiosarcomas in 92% animals (22/24). It is concluded that TP enhances the stage of sarcomogenesis initiation induced by DMH.

Animals↗

Promoting effect of testosterone propionate on experimental exocrine pancreatic tumors by 4-hydroxyaminoquinoline 1-oxide in rats.

A single intravenous injection of 4-hydroxyaminoquinoline 1-oxide in a dose of 9 mg/kg induced exocrine adenomas of the pancreas in a significantly higher rate in male than in female rats. Castration following HAQO administration diminished the incidence of the pancreatic tumors in male rats. A combined treatment with castration and weekly injections of testosterone propionate in a dose of 1 mg/rat after HAQO administration resulted in high incidence of the pancreatic tumors in both sexes. From these findings, it is concluded that testosterone can promote the induction of the pancreatic tumors in rats by HAQO.

4-Hydroxyaminoquinoline-1-oxide↗

Activation of sexual behavior by implantation of testosterone propionate and estradiol benzoate into the preoptic area of the male Japanese quail (Coturnix japonica).

Intracranial implantation of minute pellets of gonadal steroids was performed to determine neuroanatomical loci at which steroids activate sexual behavior in the Japanese quail (Coturnix japonica). In this species, systemic treatment of castrated males with either testosterone propionate (TP) or estradiol benzoate (EB) restores male-typical copulatory behavior (head grabbing, mounting, and cloacal contact movements). In addition, EB activates female-typical receptive behavior (crouching). Adult male castrated quail were implanted intracranially with 300-micrograms pellets containing TP, EB, or cholesterol (CHOL) and behavior was tested with intact males and females. Either TP or EB pellets in the preoptic area (POA) activated male-typical copulatory behavior. Mounting was specifically activated without concomitant activation of other steroid-sensitive sexual and courtship behaviors. TP and EB implants in adjacent nuclei containing receptors for these steroids and CHOL implants in POA had no effect on male-typical copulatory behavior. Eighteen percent of all males tested for female-typical receptivity crouched, but no specific effect of EB was seen at any site. The similarity of the POA sites for activation of mounting by TP and EB is consistent with the hypothesis that cells within the POA aromatize testosterone to estrogens, which directly stimulate the cellular processes leading to behavioral activation.

Animals↗

[Effect of castration and testosterone propionate on 3H-noradrenaline metabolism in different brain structures in male rats].

Experimental results demonstrated that castration in male rats led to the changes in catecholamine metabolism in various regions of the brian. In particular there is an acceleration of labeled noradrenalin- disappearance (3H-noradrenaline) from the limbic system of the hypothalamus formations. Testosterone propionate restored the initial level of 3H-noradrenaline in the mentioned structures of the brain. The data obtained indicated that adrenorecption of the rynecephalo-hypothalamic complex took part in the central regulation of the gonadotropic function of the hypophysis.

Animals↗

Effect of testosterone propionate treatment on thyrotropin secretion of young and old rats in vitro.

The aim of this study was to evaluate the influence of androgens on TSH secretion during aging in Dutch rats. Male young (2 months) and old (16-21 months) rats were castrated (Cx) or sham-operated (C) and received testosterone propionate (TP--4 mg/Kg B.W., i.m., 7 days) or vehicle. Female adult (3 months) and old (12 and 17 months) intact rats received TP or corn oil in the same dose. The rats were decapitated, trunk blood was collected and anterior pituitaries were dissected out for in vitro incubation. In Cx young male rats, only TSH pituitary content showed lower levels than in their controls. Cx TP-treated rats showed higher serum TSH and in vitro basal and TRH-induced TSH secretion, but TP only partially reversed the decrease in pituitary TSH promoted by castration. The old male rats showed lower basal in vitro TSH secretion and pituitary TSH content. In Cx old male rats, serum and basal in vitro TSH concentrations were higher than those of old controls and TP treatment further increased basal in vitro TSH secretion, as well as, stimulated TRH-induced TSH secretion. Interestingly, TP had no effect on intact young or old male rats. However, in intact old female rats, TP stimulated in vitro TSH secretion but, as observed in the intact male, TP had no effect on adult female rats. These results suggest a stimulatory role of testosterone on TSH secretion of young and old male rats. Thereafter, it seems that the testes of old rats secrete some testicular factor that inhibits TSH secretion. However, in male rats with normal testosterone levels TP treatment did not increase further TSH secretion, but in old female rats it had a stimulatory effect.

Aging↗

Cytosol estradiol receptor content in the adult rat brain after neonatal treatment with estradiol benzoate or testosterone propionate.

The effects of neonatal treatment with estrogen or androgen on the development of cytosol estradiol (E2) receptors were examined in the rat pituitary, hypothalamus and amygdala. The treatment with estradiol benzoate (EB, 100 micrograms) significantly reduced the E2 receptor content in all of these regions in both sexes. But the treatment with testosterone propionate (TP, 1 mg) to the female rats significantly decreased the E2 receptor content in the pituitary and hypothalamus but not in the amygdala. The TP treatment to the male rats decreased the E2 receptor content in the hypothalamus and amygdala but not in the pituitary. The decreased cytosol E2 receptors in the hypothalamus and amygdala seem to be implicated in preventing the normal sexual development.

Amygdala↗

Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood.

OBJECTIVE: To determine whether prenatal androgenization of the developing primate hypothalamohypophyseal unit induces irreversible changes in LH secretion. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. ANIMALS: Forty-one adult ovulatory female rhesus monkeys. INTERVENTION(S): Seventeen female rhesus monkeys exposed prenatally to testosterone propionate (female pseudohermaphrodites) and 24 normal females underwent blood sampling over two ovulatory menstrual cycles. MAIN OUTCOME MEASURE(S): Serum FSH, LH, E2, and T were determined by RIA; P was determined by enzyme immunoassay. Serum bioactive LH was measured by mouse Leydig cell bioassay. RESULT(S): Tonic immunoactive LH hypersecretion and normal FSH release occurred in female pseudohermaphrodites compared with normal females. Periovulatory immunoactive LH and FSH secretion was similar in both female types, whereas a relative increase in the amount of circulating bioactive LH to immunoactive LH was found at midcycle in female pseudohermaphrodites versus normal females. The length of the follicular phase was unaffected by prenatal androgen exposure, but the slopes of serum T and E2 concentrations versus follicular phase cycle day were significantly lower in female pseudohermaphrodites than normal females. Luteal phase length and P secretion were comparable in both types of females. CONCLUSION(S): Androgen exposure during primate neural differentiation may alter permanently the pattern of LH secretion in the presence of cyclic gonadotropin release.

Animals↗

Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is several fold larger in males than in females. When female rats were treated pre- and postnatally with testosterone propionate (TP) or with diethylstilbestrol (DES) they became anovulatory and their SDN-POA developed equivalent in size to that of normal males. Identical treatment of male rats resulted in deficient testicular development, but had no influence on SDN-POA volume. The results indicate that the gross morphological sex difference in SDN-POA volume can exclusively be controlled by the hormonal environment during the critical period of sexual brain differentiation, and that non-steroidal estrogens are just as effective as convertible androgens in stimulating SDN-POA differentiation.

Animals↗