Effect Of Testosterone Propionate Research Articles

Effects of Testosterone Propionate upon the Sexual and Aggressive Behavior of Adult Male Marmosets ( Callithrix jacchus) Castrated as Neonates

In New World monkeys of the family Callitrichidae (marmosets and tamarins), females frequently give birth to dizygotic twins. Twins share a placental circulation throughout fetal development and are hemopoietic chimeras. Despite this, there is no masculinization (freemartinism) in females which develop next to a male co-twin. It has been suggested that the organizing effects of testicular androgen upon sexual differentiation of the brain occur mainly during early postnatal development in male callitrichids, rather than in utero. However, this report demonstrates activation of masculine copulatory behavior by testosterone propionate (TP) administered to adult male marmosets ( N = 8) which were castrated in infancy (between Days 1-7). Effects of neonatal castration upon aggressive behavior during pair tests with females (high frequencies of aggression) anti intact adult males (low frequencies of aggression) were also reversed by TP treatment in adulthood. While early postnatal androgen secretion plays an important role in behavioral development in marmosets, it appears that a substantial degree of neural sexual differentiation occurs in utero in males of this callitrichid species.

The Effect of Testosterone Propionate on Growth of Broiler Chickens

The effects of testosterone propionate (TP) on body weight, tissue percentages of body weight, serum IgM, and rectal temperature (2 h postinjection) of male and female broiler chickens were investigated at 28 and 48 days posthatching. Testosterone propionate was dissolved in sesame oil and was injected at 2 mg/kg of body weight every other day, and controls were treated with sesame oil at similar volume, starting Day 7 posthatching. Administration of TP reduced (P < .05) body weight and percentages of liver, testes, and bursa of Fabricius at 28 and 48 days of age. At 28 and 48 days of age, muscle percentage and comb growth of TP-treated birds increased (P < .05) but ovarian weight was unaffected. Concentrations of IgM in serum of TP-injected birds was unchanged at Day 28, but increased (P < .05) at Day 48. Testosterone propionate did not affect percentages of bone or abdominal fat in either sex. Rectal temperature was depressed (P < .05) by TP treatment in both sexes at both ages.

Synergism of testosterone propionate with growth hormone in promoting growth of hypophysectomized rats: effect of sexual differentiation

The effect of testosterone propionate (TP), alone and in combination with porcine GH, on the growth of hypophysectomized rats was investigated. An initial study determined doses of TP and GH which would result in a synergistic response. Hypophysectomized male rats, approximately 40 days of age, received GH at doses of 5, 25 and 62.5 micrograms/day administered in two injections/day at 08.00 and 16.00 h. At all doses of GH, administration of TP at 100 micrograms/day significantly enhanced the GH-stimulated rate of growth. This growth enhancement by TP was greatest in combination with GH at 25 micrograms/day. In a subsequent study, growth responses to 25 micrograms GH/day and 100 micrograms TP/day were examined in animals with differing degrees of sexual differentiation. Sex groups were: intact males, males castrated at 11 days of age and females administered 100 micrograms TP at 3 days of age (masculinized rats), and males castrated at 2 days of age and normal females (non-masculinized rats). In all sex groups, growth of hypophysectomized rats was stimulated by GH. Genetic sex and masculinization did not influence the response to GH. Masculinized hypophysectomized rats exhibited significantly greater rates of growth and final live, empty body, liver and kidney weights than non-masculinized hypophysectomized rats. All sex groups other than normal females responded synergistically to the combination treatment of GH plus TP. Rats that experienced neonatal exposure to testosterone became programmed to respond to testosterone and demonstrated greater rates of growth and body and organ weights when administered the combination of GH plus TP. These data indicate that TP synergizes with GH to promote growth of hypophysectomized rats appropriately programmed to respond.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Testosterone Propionate and Methenolone Enanthate on the Healing of Humeral Osteotomies in the Wistar Rat

A randomized blind prospective study was carried out to determine if an anabolic androgenic steroid with a high anabolic/androgenic ratio, Group A, (1/0.05) methenolone enanthate (me), compared to an anabolic/androgenic agent with a low anabolic/androgenic ratio, Group B, (1.0/1.0) testosterone propionate (tp), compared to a control, Group C, cottonseed oil (co), affected midhumeral osteotomy healing in 100 two-month-old female Wistar rats. The rats received 4 mg/kg me, 4 mg/kg te, and equal volumes of co weekly. The rats were sacrificed at 2, 4, and 6 weeks. The entire humerus with the healing osteotomy was carefully dissected until all soft tissue attachments were stripped. The healing callus was then subjected to (1) biochemical analysis (hexosamine, hydroxyproline, and calcium), (2) biomechanical testing (progressive distraction of the callus at 1 mm/min on an electrohydraulic materials test system, model 1331, Instron Corp, Canton, MA, and (3) histology. Results of the biochemical testing demonstrated that the percentage of calcium in the healing callus at 2 weeks in group B (tp) was 7.3 +/- 1.0, and this value was greater than that in group C (co), 4.8 +/- 1.6 (p greater than .01), and greater than that in group A (me), 5.6 +/- 0.6 (p greater than .01). At 4 weeks, the percentage of calcium in the callus in group B (tp) was 6.8 +/- 1.9, in group A (me) 7.3 +/- 3.7, and these values were both greater than that in group C (co), 3.9 +/- 2.2 (p greater than .02 and .01, respectively). At 6 weeks the percentage of calcium in the callus in group B (tp) was 11.7 +/- 3.9 and in group A (me) 12.7 +/- 3.9, and again these values were both greater than that in group C (co), 6.7 +/- 2.6 (p greater than .02 and .01, respectively). The remainder of the biochemical analysis, hexosamine and hydroxyproline content, did not show a statistical difference in groups A, B, and C at 2, 4, and 6 weeks. The biomechanical studies and histology also failed to show statistical differences between the three groups at 2, 4, and 6 weeks. The conclusion of this study is that an agent with a low androgenic activity does not increase calcium callus concentrations early in the course of fracture healing compared to an agent with higher androgenic activity. As healing progresses, both agents increase the concentration of calcium in osteotomy healing. The clinical significance of this study is that agents with low androgenic activities favorably influence osteotomy healing and may be clinically useful because they lack unwanted virilizing activity.

Testosterone-induced acceleration of recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters

In this study, the effects of testosterone propionate (TP) on recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters were examined. In the first experiment, TP (5 mg/ml sesame oil; 0.1 ml) was injected subcutaneously and on alternate days in one-half of the animals subjected to crush axotomies of the facial nerve, with the second half receiving vehicle alone. An accelerative effect of TP on recovery from facial paralysis was observed near the end of the first and beginning of the second week after crush axotomy. When the dosage and frequency were doubled in the next experiment, a greater accelerative effect of TP on recovery from facial paralysis was observed. In the last experiment, castrated animals were used in order to eliminate the endogenous source of the hormone and two different modes of hormone administration, TP implants vs TP injections, were compared. The results of that experiment indicate that continuous exposure to the hormone, in the form of subcutaneous implants of 100% crystalline TP, had the most pronounced effect on acceleration of recovery from facial paralysis. In addition, no differences in the responses of the castrated, axotomized animals and the normal, axotomized animals were found. This suggests that the presence of endogenous hormone contributes little to the acceleration of functional recovery observed with TP. Finally, the time course of the accelerative effect of TP suggests that the hormone is acting primarily at the level of the facial neuron, which contains androgen receptors, and perhaps secondarily at the level of the facial muscles, which are also known to contain androgen receptors.

Effects of testosterone propionate upon habit-reversals and one-trial learning by castrated white rats.

32 male white rats, littermates from mothers of same strain, started to learn 20 habit-reversal problems at 50 days of age in an E-maze for water by the noncorrectional method. They were divided into 3 groups. Two groups of 11 each had been castrated at 32 days of age, and a group of 10 served as control. One castrated group received daily injections of testosterone propionate at 1 mg per kg of body weight 11 days after surgery. The other castrated group and the normal controls received saline. A week of preliminary training accustomed the animals to the daily routine of injection, about 30 min. before being put in the drinking box of a straight alley which they ran for water during the last 2 days. In maze learning proper, after a rat made 9 correct choices on 10 daily trials, the goal was reversed for the next problem. Early in learning, there were some fluctuations in performance, but throughout the rest of the experiment, the castrated-saline group was consistently and significantly inferior to the normals, testifying to the detrimental effect of castration upon adaptive ability in learning successive reversal problems. The fact that the castrated-testosterone group was far superior to the castrated-saline group and exhibited no significant difference from the normal-saline group shows unequivocally that testosterone propionate has a therapeutic property of raising the learning ability of the retarded, castrated white rats to a normal level. A theory is suggested.

Effects of intracranial androgen on the development of masculine ultrasonic vocalizations in the Mongolian gerbil (Meriones unguiculatus).

The effects of testosterone propionate (TP) on brain mechanisms involved in the sexual differentiation of ultrasonic vocalizations were examined in Mongolian gerbils (Meriones unguiculatus). Treatment of neonatal females with TP fully masculinized the rate of emission of the upsweep precopulatory ultrasound during adult sexual interactions with oestrous females. Intracranial implantation of small crystals of TP mixed with cholesterol (65 ng) into females 1-15 h after birth also masculinized the upsweep vocalization emitted in adulthood. Implants of TP positioned in the hypothalamic area had a significantly greater masculinizing effect than TP implants outside this region, or pure cholesterol implants. Two other sexually dimorphic vocalizations, the modulated (mainly precopulatory) and unmodulated (mainly copulatory) calls were masculinized by systemic TP, but intracranial TP had no significant masculinizing action on these calls. Genital structures of females which received neonatal injections of TP were strongly virilized in that their clitorides were lengthened and male-type cornified spines were present on the glans. Females which had received intracranial implants of TP were not virilized peripherally in adulthood. We conclude that testosterone or its metabolites have a direct hypothalamic effect on the development of masculine upsweep vocalizations. Because other vocalizations were insensitive to intracranial TP, the underlying neural tissues may have different thresholds of response to androgen.

Testosterone effects on gonadotropin response to GNRH: cows and pony mares.

Effects of testosterone propionate (TP) treatment on plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before and after an injection of gonadotropin releasing hormone (GnRH) were studied using ovariectomized cows and pony mares. An initial injection of GnRH (1 microgram/kg of body weight) was followed by either TP treatment or control injections for 10 (cows) or 11 (ponies) d. A second GnRH injection was administered 1 d after the last TP or oil injection. Concentrations of LH and FSH were determined in samples of plasma taken before and after each GnRH injection. Control injections did not alter the response to GnRH (area under curve) nor the pre-GnRH concentrations of LH and FSH in ovariectomized cows or ponies. Testosterone treatment increased (P less than .01) the FSH release in response to GnRH in ovariectomized mares by 4.9-fold; there was no effect in cows, even though average daily testosterone concentrations were 59% higher than in pony mares. Testosterone treatment reduced the LH release in response to GnRH by 26% in ovariectomized mares (P less than .05) and by 17% in ovariectomized cows (P approximately equal to .051). These results are consistent with a model that involves ovarian androgens in the regulation of FSH secretion in the estrous cycle of the mare, but do not support such a model in the cow.

Androgens enhance in vivo 2-deoxyglucose uptake by rat striated muscle.

Testosterone propionate causes a striking increase in in vivo uptake of 2-deoxyglucose by the levator ani muscle of immature male rats. Autoradiography showed the labeled 2-deoxyglucose to be uniformly distributed over the entire muscle. Liquid scintillation counting of whole muscles allowed quantification of 2-deoxyglucose uptake. After a single sc injection of testosterone propionate, no enhancement of 2-deoxyglucose uptake could be seen before 3.5 h, at which time uptake was increased 2-fold; maximum enhancement (4-fold) was attained at 12 h. 2-Deoxyglucose uptake remained elevated at twice the control value at 72 h. Muscle weight did not increase until sometime after 24 h; by 39 h, it was 50% greater than the control value; by 72 h, wet weight was double the control value. The effect of testosterone propionate probably is mediated by specific androgen receptors, since the administration of either 5 alpha-dihydrotestosterone or fluoxymesterone, potent androgens, caused severalfold increases in 2-deoxyglucose uptake in the levator ani muscle, while administration of 17 beta-estradiol, corticosterone, and etiocholanolone, an inactive metabolite of testosterone, did not. Furthermore, the effect of testosterone propionate was blocked by simultaneous administration of an androgen antagonist, cyproterone acetate. Testosterone propionate also enhanced uptake of 2-deoxyglucose in the bulbocavernosus (253% over control) and extensor digitorum longus muscles (150% over control), but not in the biceps brachii or soleus. Increased glucose uptake may be an important early step in the anabolic response of muscle to androgens.

Acceleration of the regeneration of the crushed hypoglossal nerve by testosterone

The effect of testosterone propionate (TP) on regeneration of the crushed hypoglossal nerve was studied in young adult rats. The TP treatment promoted axonal outgrowth as measured by an increase in the proportion of hypoglossal neurons labeled by retrograde transport of horseradish peroxidase injected into the tongue at selected postlesion periods compared with that in controls. The result indicated that TP exerts its effect on regeneration primarily by increasing the metabolic activity in hormone target neurons. The somatotopic organization of the hypoglossal nucleus and its projection into the major nerve branches were unaltered subsequent to crush injury. The maintenance of specificity was attributed to the intact perineurial and endoneurial sheaths which guided regenerating fibers to their original targets.

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

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

An early effect of testosterone propionate upon hypothalamic function in the neonatal rat.

Rats treated neonatally with testosterone propionate exhibit a reduced uterine growth response to estradiol administration prepubertally. This androgen-induced impairment is the consequence of developmental effects on both the ovary and the hypothalamic-pituitary complex, although the latter is the more sensitive.

Effect of testosterone on the regeneration of the hypoglossal nerve in rats

The effect of testosterone propionate (TP) on nerve regeneration was studied in young adult male rats. The TP treatment promoted axonal outgrowth of the transected hypoglossal nerve as indicated by a larger proportion of hypoglossal neurons labeled by retrograde transport after injection of horseradish peroxidase (HRP) into the tongue 2 weeks after the lesion. It was postulated that TP exerted its effect on the metabolic activity of the axotomized neurons and influenced the healing process of the nerve. The HRP axonal transport method further revealed that regeneration of the severed nerve resulted in an alteration of the somatotopic organization of the hypoglossal nucleus and a random growth of the axons into branches of the nerve in all the rats irrespective of the treatment.

The effect of testosterone propionate on wound healing in normal and castrate rats

The dependence of wound healing on testosterone was studied in normal and castrate rats by determination of wound breaking strength (WBS) in dermal wounds, by implantation of subcutaneous polyvinyl sponges (PVS) and by [ 3H]proline tracer studies. The level of testosterone achieved with various doses of testosterone propionate (TP) was assessed using the androgenic effect of this hormone on prostate and seminal vesicle weights. Exogenous testosterone propionate (0.25 – 3.0 mg/day) produced no acceleration of wound healing as measured by WBS on 14- and 21-day wounds. In castrate rats a mild inhibition of healing (15% decrease in WBS) was found in 14-day wounds but no difference was found between castrate and control in 21-day wounds. The rate of wound collagen synthesis was assessed by measuring the conversion of [ 3H]proline to [ 3H]hydroxyproline, a process essentially limited to procollagen synthesis. It was not altered by castration, or by administration of testosterone propionate (0.0625 – 1.0 mg/day) to castrate rats. Similarly, deposition of tissue in polyvinyl sponges whether measured as added dry weight or total hydroxyproline did not differ significantly between control and castrate rats receiving testosterone propionate (0–1.0 mg/day). As a method of assessing wound healing, WBS measurements produced the most consistent results. In conclusion, no longterm dependence of wound healing on testosterone was identified in the testosterone-depleted (castrate) rat although some early depression was noted, and no acceleration of the normal process resulted from exogenous testosterone administration in the normal or testosterone-depleted rat.

Testosterone affects food intake and body weight of weanling male rats

The effects of testosterone propionate (TP) on food intake and body weight were investigated using castrated prepubertal male rats. Regardless of dose (1 mg, 0.2 mg or 0.1 mg), daily injections of TP increased body weight gain and food intake during the prepubertal period (from 22 to 40 days to age). Considering previous results, the present observations suggest that in the male rat sensitivity to the effects of gonadal hormones on feeding develops earlier than in females.

Effects of testosterone propionate on hindlimb-immobilized rats.

Forty albino male rats were randomly divided into 4 groups of 10. Group I served as the nonimmobilized control and received daily placebo injections of sesame oil. The rats in group II were castrated, their hindlimbs were immobilized using a plaster cast, and they received daily injections of sesame oil. The group III rats were also castrated and casted but received a daily injection of 5 mg testosterone propionate. The animals in group IV were not castrated but were casted and received daily testosterone propionate injections. The duration of each treatment was 15 days for each rat. The gastrocnemius, quadriceps, soleus, and cardiac muscles were weighed after treatment. O2 consumption capacity (QO2), citrate synthase activities, and percentages of water were measured in the gastrocnemius, quadriceps, and cardiac tissues. Along with the atrophy of muscle and reduction in body size, the immobilization significantly reduced the aerobic capacity of affected muscle groups and cardiac tissue. The greatest reductions in body weight, muscle size, heart size, and QO2 were seen in the castrated group that received only placebo injections of sesame oil. The anticatabolic effects of the anabolic steroid were evident in groups III and IV. The results indicate that hindlimb immobilization not only causes severe atrophy in those muscles immobilized but has an overall catabolic effect on the animal. Testosterone, or the lack of it, can significantly affect the amount of muscle atrophy.

Dose-dependent effects of testosterone on feeding and body weight in male rats

The effects of testosterone propionate (TP) on food intake and body weight were investigated using adult male Sprague-Dawley rats. Daily injections of a high (1 mg) or a low (0.2 mg) dose of TP were administered for 8 weeks beginning immediately after castration. Both doses of TP reduced body weight gain during the first 4 weeks of treatment, but long-term treatment with the low dose stimulated food intake and body weight gain. Injections of the high dose of TP reduced body weight gain and food intake over the 8 weeks of treatment. These findings suggest that the effects of TP on body weight and feeding are dose dependent. Considering previous data, a maintenance paradigm of hormone replacement seems to maximize the anorexic and weight-reducing effects of TP treatment.

The effects of androgen and estrogen on thymidine kinase and tissue plasminogen activator in the prostate of immature rats (author's transl)

The effect of testosterone propionate (TP) or estradiol-17 beta (E2) on the activities of thymidine kinase (TK) and tissue plasminogen activator (Act) in the prostates of 22 day old immature SD rats was studied. The Tailor and fibrin plate methods were applied to measure the activities of TK and Act respectively. Act activity was expressed in terms of the Urokinase International Unit. After a single TP injection im, TK activity began to increase at 24 h and peaked at 48 h followed by a rapid decrease. The maximum activity, 40.0 +/- 11.5 pmol/mg protein/15 min, was 50 times higher at 48 h and peaked at 96 h, with a subsequent decline to the control value within 14 days. The maximum Act activity, 5.1 +/- 0.4 U/prostate, was 1.6 times the control value. The activities of both TK and Act altered depending on TP doses, 1 mg/100 g BW of TP brought about their maximum activities at 48 h and 96 h respectively. Three TK isozymes were obtained from the prostates by DEAE-cellulose column chromatography. Fraction A, which was eluted in O M NaCl, differed from other isozymes in that its activity was only slightly suppressed by dCTP and was elevated most conspicuously after TP injection. Elevated activities of both TK and Act after TP injection were completely inhibited by Puromycin or Actinomycin D. The results of the present experiment demonstrated that TK and Act were synthesized in the prostate cells after TP injection and were androgen dependent. E2 did not inhibit the elevation of TK and Act activities by TP injection. In the present study estrogen showed a synergetic effect with androgen on these two activities, especially TK, in the rat prostate.

Testicular function of actively immunized male rats with LH releasing hormone (LHRH): a possible role of prolactin on regulation of spermatogenesis.

The effect of testosterone propionate (TP) on the recovery of spermatogenesis was compared in 3 types of experimentally induced gonadotropin-deficient rats; 1. hypophysectomized rats, 2. rats actively immunized to LHRH and 3. hypophysectomized and immunized rats bearing a pituitary isograft. In order to immunize animals to LHRH, deamidated LHRH conjugated with BSA (LHRH-BSA) was injected intradermally to male rats 4 times at 2 week intervals and additional booster injections continued once a month. Anti-LHRH titer was the highest on the 12th week and the titer remained at a relatively high levels thereafter. A remarkable decrease in testicular weight and testosterone production was achieved in 10 weeks associated with a drop in serum LH and FSH levels. In long term immunized rat (LIM rats) which had been immunized for more than 3 months, testicular atrophy advanced to a similar extent to that in long term hypophysectomized rats (HX rats). The administration of TP (1 mg/day) sc for 30 days restored spermatogenesis in LIM rats. The simultaneous administration of anti-LH and -FSH sera in addition to TP did not affect the restoration of spermatogenesis in LIM rats. The same TP treatment in HX rats, however, failed to restore spermatogenesis. Spermatogenesis was reinitiated after TP treatment if immunized-hypophysectomized rats received a pituitary isograft. Though the serum PRL level in LIM rats was one fifth of that in normal rats, a 2.5-fold rise in the PRL level was observed after TP treatment. These results suggest that PRL is involved in the process of spermatogenesis.

Effect of testosterone propionate on protein synthesis by two-dimensional electrophoresis in rat ventral prostate.

Two-dimensional polyacrylamide gel electrophoresis has been used to map the pattern of protein synthesis in rat ventral prostate from both castrate and testosterone treated animals. Proteins were detected by fluorography of 35S-methionine incorporation. In the soluble or cytosol fraction, four major proteins that have molecular weights less than 25,000 and isoelectric points (pI) less then 6.0 and one than has a molecular weight above 30,000 and pI 6.6 are under androgen control. One of these proteins with molecular weight 12,000 and pI 5.4 also appears in the microsomal fraction. Using nonequilibrium pH gradient electrophoresis, soluble proteins of pI greater than 7.0 were investigated. One major protein of 20-25,000 daltons and pI 8.0 appears to be androgen dependent. The ventral prostate from castrate synthesized proteins which are not detectable in androgen stimulated castrates.