Testosterone Profiles Research Articles

Uptake and depletion of plasma 17α-methyltestosterone during induction of masculinization in muskellunge, Esox masquinongy:: Effect on plasma steroids and sex reversal

Oral administration of 17α-methyltestosterone (MT) was used to induce masculinization of sexually undifferentiated muskellunge, Esox masquinongy. Three groups of muskellunge (mean weight, 2.5 ± 0.6 g) were submitted to MT treatment (15 mg of MT/kg) for 60 days. An additional one group was used as a control (hormone-free diet). Food was distributed over a 10-h period by using automatic belt feeders. Blood was sampled in both control and treated fish at different intervals during and after feeding: before (0 h), at 3 h, 6 h, and cessation of feeding (10 h), and after a fast of 22 h (32 h). MT had no significant effect on growth and survival in muskellunge 6 months after the treatment. Concentrations of plasma MT increased during the feeding period and reached their maximum levels 6 or 10 h after starting feeding. This rapid increase of MT indicated a rapid absorption of this steroid. Plasma MT levels then declined and reached a radir by 22 h after cessation of feeding, suggesting that MT is rapidly metabolized and excreted. The profiles of plasma testosterone during the MT treatment did not differ significantly between control and MT-treated groups. During and after the MT treatment, the concentration of plasma testosterone did not differ significantly between control and MT-treated groups. Moreover, no sexual dimorphism of testosterone levels was observed. Six months after treatment, the sex ratio in MT-treated groups (33% males, 62% females, and 5% intersex) was opposite to control (70% and 30%, respectively) and differed significantly. This suggests that at 15 mg of MT/kg over 60 days, a paradoxical feminization took place.

Effects of hypercholesterolaemia on Leydig and Sertoli cell secretory function and the overall sperm fertilizing capacity in the rabbit.

The effects of hypercholesterolaemia on testicular endocrine and exocrine function were evaluated. The influence of hypercholesterolaemia on sperm quality, quantity, and fertilizing potential was also determined. Ten mature rabbits (group A) were fed chow containing 3% cholesterol for 12 weeks. Ten control rabbits (group B) were fed normal chow for the same period. At the end of the experimental period testosterone profiles and sperm parameters were evaluated and the sperm reproductive potential was assessed by in vitro fertilization (IVF) techniques. Peripheral serum testosterone responses to testicular stimulation with human chorionic gonadotrophin, androgen-binding protein activity in testicular cytosols, sperm concentration, sperm motility, length of sperm midpiece, and IVF outcome were all significantly lower in group A than in group B. In contrast, serum cholesterol concentrations were significantly higher in group A. There were no significant differences in either testicular versus intra-abdominal temperature differences or cholesterol concentrations in seminal plasma or testicular tissue between groups A and B. The results suggest that hypercholesterolaemia has a detrimental effect on Leydig and Sertoli cell secretory function, spermatogenesis, epididymal sperm maturation process, and the overall sperm fertilizing capacity.

Transdermal Testosterone Delivery: Comparison Between Scrotal and Nonscrotal Delivery Systems

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs), Testoderm®, designed to deliver testosterone through scrotal skin, and Androderm®, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is ∼13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration–time curve (AUC0–28) [665 versus 3208 (ng/dl) × hr] between these T-TDSs. However, there is no difference in time to reach Cmax, mean residence time, and daily-delivered-dose-normalized Cmax and AUC0–28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (∼13-fold) between the nonscrotal and scrotal T-TDSs.

Plasma testosterone profiles, semen characteristics, and artificial insemination in yearling and adult captive Mallard ducks (Anas platyrhynchos)

Testosterone profiles and semen characteristics were determined using yearling and adult captive wild-strain Mallard (Anas platyrhynchos) drakes. Wild-strain Mallard hens were artificially inseminated by modifying a technique developed for domesticated poultry. In both adult and yearling drakes, there was a change in the concentration of circulating plasma testosterone during the reproductive season. Testosterone concentrations increased from basal levels in March, peaked in April, and decreased to basal levels in May. The decrease in testosterone concentration to basal level was 2 wk earlier in yearlings than in adults (P < 0.05). The decrease in testosterone concentration was associated with the onset of postnuptial molt. Semen volume (0.04 to 0.08 mL) and semen concentration (approximately 1.32 x 10(9) spermatozoa per milliliter) were not different between adult and yearling drakes (P > 0.05). Overall mean fertility for yearling and adult drakes obtained with artificial insemination was 70.4%. These results suggest that artificial insemination may be used successfully in the propagation of captive wild-strain Mallard ducks.

8-OH-DPAT Interacts With Sexual Experience and Testosterone to Affect Ejaculatory Response in Rats

Studies investigating the effect of 8-OH-DPAT (DPAT) on male sexual response have typically used subjects having variable sexual experience and levels of testosterone, factors known to independently influence male sexual behavior. This experiment examined the role of these two variables in the mediation of DPAT effects on sexual behavior. One hundred and six castrated males, half of whom received sexual experience, were tested with an effective dose of 8-OH-DPAT (0.1 mg/kg) or saline. In addition, males were tested under one of three regimens of testosterone. Results indicated that DPAT and testosterone exerted independent effects on ejaculatory measures, and along with sexual experience, showed interactive effects as well. When testosterone (T) levels were substantially below normal, DPAT showed no effect. When T reached threshold levels, the DPAT effect was limited to sexually experienced males. At high T levels, both experienced and naive males exhibited strong effects from DPAT. In contrast with ejaculatory measures, mounting and intromitting behaviors were relatively unaffected by DPAT. These results emphasize the importance of specifying both the animal’s sexual history and its testosterone profile in studies investigating pharmacological effects on sexual response.

Tamoxifen-induced light and electron microscopic changes in the rat testicular morphology and serum hormonal profile of reproductive hormones

The effects of oral administration of tamoxifen at doses of 40 and 200 μg/kg/day on testicular histology, testicular ultrastructure and serum hormonal profile were studied. The drug was administered to adult male rats over a period of 90 days and the effect was assessed at 10-day intervals. The morphometry, microscopic structures of the testis, including ultrastructure and daily sperm production rate, were evaluated. The hormone profiles of luteinizing hormone (LH), follice-stimulating hormone (FSH), testosterone, and estradiol were studied. The testes from treated animals showed disorganization of tubular elements with increased intercellular space. At day 50, the changes were extensive including presence of phagosomes. Morphometric studies showed a reduction in the spermatid and spermatozoan population (69.3%) with no changes in tubular diameter. The mean Leydig cell area was significantly lowered at day 50, at both doses. The daily sperm production rate was reduced as compared with controls. An array of degenerative changes were revealed by ultrastructural studies. The changes were extensive at day 50 at both doses. The characteristic features were lost in most of the cells with phagolysosomes becoming abundant. The cytoplasm of the cells was dense with poorly defined cytoplasmic organelles. Circulating LH levels were not modified at the 40 μg/kg/day dose but at 200 μg/kg/day, LH levels were significantly decreased. Initial transitory rise in FSH was seen with both doses. Both doses of tamoxifen decreased testosterone levels. Changes in the circulating estradiol levels were inconsistent, and no apparent relationship between dose and days of treatment was observed. Thus, this study supports our thesis of tamoxifen as a potential male contraceptive agent.

Absence of an Inhibitory Vasopressinergic Tone on LH Release in Pubertal Male Rhesus Macaques

During puberty, primates begin to secrete LH, and presumably GnRH, at night and then eventually throughout the day as they mature. We examined the role of vasopressin, a putative inhibitor of the GnRH pulse generator, on LH secretion in pubertal male macaques both during the day when the GnRH pulse generator was not active and during the night when pulsatile LH secretion was observed. As has been found in other primates, LH and testosterone levels were low during the day and elevated at night. A potent vasopressin receptor antagonist (VPa) was administered during the middle 5 h of a 15-hour daytime or nighttime blood collection period to determine the effects on LH, testosterone and cortisol secretion. Both during the day and night, cortisol secretion was elevated during VPa infusion, suggesting that this V1a receptor antagonist has agonist activity on the V1b receptor in the pituitary involved in vasopressin-stimulated corticotropin release. Mean LH levels during VPa infusion were not different from the control period for that group during the day when LH secretion was absent. Mean LH levels were significantly higher (p < 0.05) than pre-VPa LH levels at night when pulsatile LH secretion was observed. However, LH levels at night during VPa were not higher than levels in untreated animals at the same time. The results of these studies demonstrate that LH and testosterone profiles are similar to those observed in human males during the pubertal transition and suggest that the absence of daytime gonadotropin release during puberty is not due to inhibitory vasopressinergic tone on the GnRH pulse generator.

Abrupt changes in photoperiod affect age at maturity, timing of ovulation and plasma testosterone and oestradiol-17 β profiles in Atlantic salmon, Salmo salar

Atlantic salmon ( Salmo salar L.), reared in sea cages for 18 months (age 36 months from hatching), were exposed to natural light (NL, 61°N), or continuous additional light from January (ALJ) or March (ALM) until July. On July 13, the fish were moved to indoor raceways with brackish water (2–19‰) and ambient temperature (declining from 13.0 to 5.6°C). Fish from each treatment were subjected to either simulated natural photoperiod (SNP), continuous light (24L), or short photoperiod (8L=8 L:16D), creating a total of nine experimental groups with approx. 50 fish in each. The proportion of sexually maturing females was reduced from 91% in the NL groups, to 67% and 9% in the ALM and ALJ groups, respectively ( p≤0.005). A similar reduction was observed among the males, from 74% in the NL groups, to 57% and 16% in the ALM and ALJ groups, respectively ( p≤0.001). Ovulation commenced in late October in the control group (NL-SNP). Compared with control, median ovulation time was advanced by 5, 4 and 3 weeks in the ALM-8L, NL-8L and ALM-SNP groups, respectively, whereas ovulation was delayed by 1 and 6 weeks in the ALM-24L and NL-24L groups, respectively. The altered timing of ovulation among the groups was paralleled by similar shifts in the seasonal plasma oestradiol-17 β and testosterone profiles. Survival of eggs to the eyed stage was lower in the ALM-8L group (mean=64.2%) compared with the NL-SNP group (mean=92.5%), indicating a negative effect on egg quality in the most advanced group. Although abrupt changes in photoperiod can be used to control timing of ovulation in Atlantic salmon to obtain off-season eggs, the decrease in egg survival and proportion of maturing fish may set constraints on how much maturation can be advanced by use of continuous light during winter and spring. However, the effect on age at maturity may also be exploited to reduce the problem with unwanted early maturation in salmon farming.

Transdermal testosterone delivery in castrated Yucatan minipigs: pharmacokinetics and metabolism

The feasibility of using the castrated Yucatan minipig as a hypogonadal animal model to investigate the transdermal controlled systemic delivery of testosterone was studied. During a 24 h application of a testosterone transdermal delivery device (T-TDD), serial blood samples were withdrawn from the minipigs, without anesthesia, at predetermined time intervals and the plasma concentrations of testosterone as well as its major metabolites, dihydrotestosterone and estradiol, were assayed by radioimmunoassay. The compartmental pharmacokinetic modeling analysis of the plasma profiles of total testosterone indicated that as much as 92% of the total testosterone dose released from the T-TDD had been delivered transdermally into the systemic circulation during the initial rapid input period (the first 11 h of the application), while only 8% was delivered during the slow input period (up to 23 h). Good correlation was observed between the in vivo input doses [1.9 (±0.2), 4.8 (±0.2) and 6.4 (±0.5) mg/day], determined by the Wagner-Nelson equation, and the daily doses released [1.9± (0.2), 4.7 (±0.2) and 6.6 (±0.5) mg/day, respectively, for 1, 2, and 3 units of T-TDD]. While the in vivo rate of input in the castrated minipigs was observed to be similar to that in hypogonadal men treated with the T-TDD during the first 8 h period, the input rate was found to be slower during the last 12 h. The agreement could suggest that the mechanism for the transdermal systemic delivery of testosterone in the castrated minipig could be similar to that in the hypogonadal men. However, the plasma testosterone profiles attained in the castrated minipigs were observed to be similar to, but slightly lower than that in the hypogonadal men reported in the literature. The Δ C max (baseline normalized peak plasma concentration) and Δ C avg (baseline normalized average plasma concentration) data in the castrated minipigs were 40 and 44%, respectively, of that in hypogonadal men. The ~2.4 fold lower values in Δ C max and Δ C avg data could result from the difference in the clearance rate of testosterone which is ~2.8 fold higher in minipigs than in the human. Despite the difference in clearance rate, the castrated minipigs could be a suitable large animal model for studying the pharmacokinetics of testosterone delivered transdermally in humans with hypogonadism.

Prostate cancer and tumor stage-dependent circadian neuroendocrine disturbances

The aim of this study was to analyze the circadian profiles of central and peripheral circulating hormones in patients with unoperated primary localized prostate cancer and to test whether any specific endocrine disturbances occur in the presence and/or during the growthf these tumors. The hormones analyzed in serum included melatonin, total testosterone, luteinizing hormone (LH), prolactin, Cortisol, total thyroxine, and thyroid stimulating hormone (TSH). Blood was collected at 4-hourly intervals over one complete 24-h cycle from 18 patients with prostate cancer, from 20 patients with unoperated benign prostatic hyperplasia (BPH) serving as age-matched controls, and from 18 young men. The single cosinor method was used for the mathematical analysis of circadian rhythmicity. The most obvious result was that the circadian amplitude of melatonin was drastically depleted in prostate cancer patients compared to those with BPH (-71%). Prostate cancer patients with primary tumors staged as T2 and higher showed extremely low melatonin levels, leading to the loss of detectable circadian rhythms. A similar trend was observed for prolactin in prostate cancer patients. A further prominent finding was that the MESOR (rhythm-adjusted 24-h mean) of TSH was clearly depleted in prostate cancer patients compared to those with BPH (-46%), showing very low values in patients with T2 and T3/T4 tumors in spite of normal total thyroxine concentrations. The circadian profiles of total testosterone, LH and Cortisol did not exhibit any marked cancer-specific changes, indicating that neither the pituitary-gonadal nor the pituitary-adrenal axis was affected by malignant growth. The observed circadian endocrine disturbances in prostate cancer patients thus show clear central endocrine disturbances. It is at present unclear whether these changes may bear any direct functional significance for the progression and prognosis of prostate cancer. It is, furthermore, unknown how these changes are generated and whether the depression of pineal melatonin secretion may be functionally involved in the observed disturbed circadian secretion of prolactin and TSH.

High Testosterone Prior to Song Crystallization Inhibits Singing Behavior in Captive Yearling Dark-Eyed Juncos (Junco hyemalis)

In passerine birds, song is considered crucial in advertising reproductive and territorial status to conspecifics. Variation in the quality and frequency of song may be influenced by hormonal effects during the individual's development. This variation in turn may affect the function and potency of song. We studied the influence of testosterone on vocal production in first-year male dark-eyed juncos (Junco hyemalis), using subcutaneous silastic implants filled with testosterone. Subjects were visually but not acoustically isolated from one another and after capture had no exposure to female or adult male models. Implants were administered when subjects were in the plastic song phase (i.e., after they had begun to sing but before song was fully crystallized). Control males (C males) received empty implants. Experimental males were of two classes: TI males received one dose of testosterone (a single 10-mm implant), and TII males received two doses. Testosterone implants kept plasma levels high well into the breeding season, whereas in nature, levels normally drop after territorial acquisition and pair formation. Control males sang at higher rates than testosterone-treated males of both classes and had the greatest number of song types. This inhibitory effect of testosterone on vocal production suggests that disturbance of seasonal profiles of testosterone in birds may interfere with the production of species-typical song.

Seminal cytokine concentrations (IL-1beta, IL-2, IL-6, sR IL-2, sR IL-6), semen parameters and blood hormonal status in male infertility.

Several lines of evidence indicate that cyokines are involved in male fertility. They are secreted by different parts of the male genital tract and may exert effects on steroidogenesis, spermatogenesis and sperm functions. We measured the concentrations of interleukins (IL-beta, IL-2, IL-6) and those of interleukin soluble receptors (sR IL-2, SR IL-6) in semen of fertile subjects (n = 21) and of patients with a range of andrological diseases (n = 119). The seminal concentrations of cytokines were analysed according to semen parameters as well as to the blood hormonal profiles of follicle stimulating hormone, luteinizing hormone and testosterone. An increase of IL-1beta was observed in the group of patients with infertility. No difference was found between the different subgroups defined on the basis of progressive motility, percentage of abnormal forms and diagnosis of infection. The seminal cytokine concentrations were independent of the blood hormonal status. Our data suggest that the determination of interleukins (-1beta, -2 and -6) or interleukin soluble receptors (sR IL-2, sR IL-6) in human spermatozoa does not provide convenient information in male routine infertility work-up.

Twenty-four-hour profiles of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels: a semilongitudinal study throughout puberty in healthy boys.

To follow and correlate gonadotropin and sex steroid changes throughout puberty, 24-h profiles of LH, FSH, testosterone, and estradiol were taken on several occasions for between 2-9.5 yr in 12 healthy boys, aged 8.7-18.2 yr. Serum concentrations of LH and FSH were measured every 20 min, whereas testosterone and estradiol were measured every 2-4 h during the 24-h period. The prepubertal boys (Tanner stage 1) were subdivided into two groups: Pre 1, with a testicular volume of 1-2 mL, and Pre 2, with a testicular volume of 3 mL. Pubertal stages were classified, according to testicular volume, as early puberty (pubertal stage 2; 4-9 mL), midpuberty (pubertal stages 3-4; 10-15 mL), and late puberty (pubertal stage 5; > or = 16 mL). Mean levels of LH and FSH increased with pubertal development, although the increase in LH was greater than that in FSH. These increases were due to elevated basal levels of LH and FSH as well as to increases in the number of peaks and the peak amplitudes of LH. No diurnal rhythm was found in boys at stage Pre 1. Thereafter, a clear diurnal rhythm appeared for LH, and later in puberty, an ultradian rhythm was superimposed, as shown by time-sequence analyses. A diurnal rhythm also existed for FSH, but was much less marked than that for LH despite a clear covariation between LH and FSH, as shown from cross-correlation studies. Testosterone also showed diurnal variations from the late prepubertal stage, followed by increasing levels during both day and night in puberty. We conclude that during puberty, gonadotropin levels rise differently for LH and FSH, which may be due to the development of differences in feedback mechanisms. Despite covariation between LH and FSH, only LH showed a clear diurnal variation. In parallel, nocturnal variations in testosterone and estradiol were found. Changes in mean levels of LH, testosterone, and estradiol as well as their mean daytime and nighttime levels follow each other from the prepubertal stages to late puberty.

Twenty-Four-Hour Profiles of Luteinizing Hormone, Follicle-Stimulating Hormone, Testosterone, and Estradiol Levels: A Semilongitudinal Study throughout Puberty in Healthy Boys

Twenty-Four-Hour Profiles of Luteinizing Hormone, Follicle-Stimulating Hormone, Testosterone, and Estradiol Levels: A Semilongitudinal Study throughout Puberty in Healthy Boys

Three-month depot of goserelin acetate: clinical efficacy and endocrine profile

Objectives To compare the pharmacodynamics and tolerability of the new goserelin acetate 10.8-mg depot with the 3.6-mg depot in patients with advanced prostate cancer during the first 3 months of therapy. Methods One hundred sixty patients were randomized in two comparative studies to receive either the 10.8-mg goserelin acetate depot every 12 weeks or the 3.6-mg goserelin acetate depot every 4 weeks for 12 weeks and then the 10.8-mg depot every 12 weeks thereafter. Data for pharmacodynamic assessments were collected prospectively, whereas clinical response data were collected retrospectively. Results Serum testosterone profiles of the 10.8-mg goserelin acetate depot and the 3.6-mg goserelin acetate depot were similar; testosterone levels in both groups fell below castrate levels by day 21 after administration. Decreases in serum prostate-specific antigen level after 3 months of therapy were also similar in both groups: 94% with the 10.8-mg depot and 92.5% with the 3.6-mg depot. For all patients, the median time to progression was 152.7 weeks and the median time to death was 213.6 weeks. The safety profile of the 10.8-mg goserelin acetate depot was similar to that of the 3.6-mg depot; hot flashes was the most common adverse event. The incidence of injection site reactions was very low (2 [0.3%of 614 administrations). Conclusions The new 10.8-mg depot was pharmacodynamically equivalent to the current 3.6-mg depot and was well tolerated, both locally and systemically. The observed times to progression and survival were as expected in this patient population. The 10.8-mg goserelin-acetate depot provided a dosing schedule that was convenient for the patient and the physician, and it has the potential to reduce health care costs while maintaining the quality of life in patients being treated for advanced prostate cancer.

Testosterone secretion, musth behaviour and social dominance in captive male Asian elephants living near the equator.

Testosterone concentrations were measured in blood samples collected weekly over a 5 year period from six adult (19-40 year old) male Asian elephants (Elephas maximus maximus) living in captivity in Sri Lanka (7 degrees N), to investigate the relationship between androgen secretion and the occurrence of musth (temporal gland secretion, drip urination and aggressive behaviour). The testosterone profiles were very variable both within and between animals. Long-term phasic changes in blood concentrations of testosterone, associated with periods of musth, occurred in three of the six elephants, with the most pronounced cyclicity in the oldest animal. Musth occurred annually after periods of high androgen secretion and there was a positive correlation between the duration of musth and mean concentrations of testosterone during the previous 2 months. The time of musth, while consistent for an individual, was variable between animals. In four bulls living within one social group, there was a positive correlation between social rank and mean concentrations of testosterone over the 5 year study, and only the dominant animal showed periodic musth. Short-term changes in testosterone concentrations occurred in blood samples collected every 15 min for 7 h, and following the injection of 20 micrograms GnRH, consistent with regulation through the pulsatile secretion of LH. Overall, the results support the view that fully mature male Asian elephants living near the equator express an asynchronous, cyclical, circannual pattern of gonadal activity, with the cyclical pattern developing progressively from 20 to 40 years of age. The periodic increase in testosterone secretion during the gonadal cycle induces the development of musth; however, androgen withdrawal following a period of hypersecretion may be the cause of some aspects of musth behaviour (aggression, unpredictability, disobedience) which make bull elephants very difficult to manage in captivity.

Secretory profiles of LH and testosterone in pubescent male goat kids

Secretory profiles of peripheral plasma luteinising hormone (LH) and testosterone (T) in pubescent male goat kids were determined in serial blood samples collected at 15 min intervals for a 6 h period fortnightly over a 4 month period by radioimmunoassays. In four kids, after remaining at a high level at 12–15 weeks of age, the baseline concentration of LH declined until 20–21 weeks, when it increased to a maximum value. Similarly, after a maximum value of 5.21 ng ml −1 at 12–13 weeks of age, the mean LH concentration decreased, with another increase at 20–21 weeks of age. The maximum pulse frequency was observed at 12–13 weeks of age. After lower values at 14–19 weeks of age, it increased at 20–21 weeks of age. Likewise, the pulse magnitude was highest at 12–13 weeks of age and decreased with advancing age. In two kids, the baseline T concentration was 0.35 ng ml −1 at 12 weeks of age, and had increased to a mean of 2.01 ng ml −1 at 20 weeks. The mean T concentration at 12–16 weeks of age ranged between 1.20 and 1.24 ng ml −1 and increased at 20 weeks, reaching a peak value at 26 weeks of age. After relatively higher values at 12 weeks of age, the pulse frequency remained low between 14 and 18 weeks of age and increased thereafter. The pulse magnitude at 12 weeks of age was 3.60 ng ml −1, it fluctuated between 14 and 18 weeks and then increased consistently to reach the highest value of 7.18 ng ml −1 at 26 weeks of age. It appears that an increase in LH mean concentration, and pulse magnitude and frequency around 12 weeks of age stimulated testicular growth and induced spermatogenesis in pubescent goat kids.

Brain–Pituitary–Gonadal Axis during Early Development and Sexual Differentiation in the Rainbow Trout,Oncorhynchus mykiss

Profiles of testosterone, 11-ketotestosterone, androstenedione, and estradiol were determined by RIA, and immunocytochemical techniques were employed to identify gonadotropin (GTH) I and II and gonadotropin releasing hormone (GnRH) in monosex and mixed sex populations of rainbow trout from 1 to 126 days postfertilization (dpf). Steroid levels were relatively high at 1 dpf and declined until 25 dpf. At 30 and 48 dpf (hatching) steroid levels increased slightly before they fell by 78 dpf and remained relatively constant thereafter. Trends toward differences in steroid content between males and females became evident around the time gonadal differentiation was histologically discernible (78 and 90 dpf). GTH I was present in the proximal pars distalis at all dates (48–126 dpf), whereas GTH II was not detectable. GnRH was found at all dates (48–126 dpf) and was distributed in several areas of the brain including the nucleus preopticus periventricularis, nucleus lateralis tuberis, and the pituitary in the region where GTH I was found. No differences were seen between males and females in the timing of appearance, localization, or intensity of staining of these peptide hormones. Given that the brain–pituitary–gonadal axis seems to be intact during the process of sexual differentiation and the fluctuations of steroid levels during this process, sex steroids may play the driving role for sexual differentiation of rainbow trout.

Neonatal Phenobarbital-Induced Persistent Alterations in Plasma Testosterone Profiles and Testicular Function

Daily sc injections of phenobarbital at anticonvulsant therapeutic doses for the rat (40 mg/kg) for the first 7 days of life resulted in below normal levels of serum testosterone from around birth to before puberty, normal levels during puberty and above normal levels of the androgen after puberty and in adulthood. Cluster analysis of the plasma testosterone secretory profiles obtained at 15-min intervals from phenobarbital-treated rats at 65 and 165 days of age revealed a significant increase in both the peak amplitudes and their durations resulting in a 100% increase in the amount of hormone secreted during the peak periods. In general, most of the rats (control and experimental) secreted testosterone as two large peaks, each 3 to 4 hr in duration, during the 10-hr lights-on collection period. In addition to permanently disrupting the ultradian profiles of plasma testosterone, neonatal exposure to the barbiturate altered testicular responsiveness to steroidogenic regulatory agents. That is, neonatal exposure to phenobarbital enhanced the responsiveness to exogenous hCG as measured by an above-normal increase in testosterone concentration. Moreover, phenobarbital-induced reductions in serum testosterone levels were delayed in adult rats neonatally exposed to the barbiturate. Whereas a single challenge dose of phenobarbital (1 or 10 mg/kg) reduced serum testosterone concentrations in control animals by almost 80% within 3 hr, a decline in serum androgen levels in the neonatally phenobarbital exposed males was not observed until 12 hr after the challenge dose. These results indicate that postpartum exposure to therapeutic levels of phenobarbital can permanently disrupt testosterone secretory profiles and alter pathways regulating testicular steroidogenesis.

A New Long Acting Formulation of the Luteinizing Hormone-Releasing Hormone Analogue, Goserelin: Results of Studies in Prostate Cancer

Purpose To assess the pharmacodynamic equivalence of the new 10.8 mg. goserelin depot with the current 3.6 mg. depot 3 studies were performed in patients with advanced prostate cancer. Materials and Methods In 2 comparative studies 160 patients were randomized for dosing every 12 weeks using the 10.8 mg. depot or every 4 weeks using the 3.6 mg. depot. In the noncomparative study 35 patients received the 10.8 mg. depot. Blood sampling for serum testosterone and evaluation of toxicity was done during the 48-week study period. Results Serum testosterone profiles of the 10.8 and 3.6 mg. goserelin depots were similar with testosterone levels decreasing into the castrate range by day 21 after depot administration. The safety profile of 10.8 mg. goserelin is comparable to that of the current monthly depot with the main side effects related to androgen deprivation. Conclusions The new long acting depot was pharmacologically equivalent, and well tolerated locally and systemically, and will offer added convenience to patients and health care personnel.