Biomedical subjects

G F Weinbauer

Publications and source records attributed to G F Weinbauer.

At least 91 records · Page 5Linked to original sources

PubMed1991

Effects of flutamide on testicular involution induced by an antagonist of gonadotrophin-releasing hormone and on stimulation of spermatogenesis by follicle-stimulating hormone in rats.

The effects of combined treatment with an antagonist of gonadotrophin-releasing hormone (ANT) and the antiandrogen flutamide (FL) on spermatogenesis were studied in the presence and absence of exogenous follicle-stimulating hormone (FSH). After treatment for 2 weeks, the combination of ANT (RS 68439, 450-500 micrograms/kg per day, s.c.) with 10, 20 or 40 mg FL/day, s.c. was as effective as ANT plus the Leydig cell toxin ethane dimethane sulphonate (75 mg/kg per week, i.p.) in terms of reduction in weight of testes, epididymides and seminal vesicles. Thus, a daily dose of 10 mg FL/kg was sufficient to block the androgen action in the testes of ANT-treated rats. In a second experiment, rats received ANT and ANT+FL (10 mg/kg) alone or in combination with a highly purified human FSH preparation (5 or 10 iu, twice a day) for 2 weeks. FSH did not affect testosterone concentration or weight of epididymides and seminal vesicles, but ANT+FL markedly enhanced the ANT-induced reduction of testis weight, seminiferous tubule diameter and numbers of germ cells, as revealed by qualitative and quantitative analysis of testis histology. In the absence of FL, testis size and numbers of germ cells, including elongated spermatids, were increased by FSH. In the presence of FL, the effects of FSH were less pronounced with respect to the germ cells, in terms of both numbers of cells and the effective dose of FSH. Irrespective of treatment with FL, exogenous FSH increased the inhibin concentrations in serum, indicating that Sertoli cells remained responsive to FSH. From the present study it is concluded that (i) FL accelerates ANT-induced testicular involution, (ii) FSH has a role in adult spermatogenesis and (iii) the effects of FSH on advanced germ cells are influenced by androgens.

Androgens↗

PubMed1991

Effect of administration of testosterone and gonadotrophin-releasing hormone (GnRH) antagonist on basal and GnRH-stimulated gonadotrophin secretion in orchidectomized monkeys.

The aim of the present investigation was to investigate the effects of testosterone on basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin secretion in the presence and absence of a GnRH antagonist in a non-human primate model (Macaca fascicularis). Orchidectomized animals were used in order to avoid interference by testicular products other than testosterone involved in gonadotrophin feedback. Concomitant and delayed administration of testosterone at doses that provided serum levels either within the intact range (study 1) or markedly above that range (study 2) did not influence the suppression of basal gonadotrophin release induced by the GnRH antagonist during a 15-day period. To assess the possible effects of testosterone treatment at the pituitary level (study 3) GnRH stimulation tests (500 micrograms) were performed before and on days 8 and 15 of treatment with high-dose testosterone and GnRH antagonist alone or in combination. Testosterone alone abolished the gonadotrophin responses to exogenous GnRH observed under pretreatment conditions. With GnRH antagonist alone, an increased responsiveness (P less than 0.05) to GnRH was seen on day 8 and a similar response compared with pretreatment on day 15. Following combined treatment with GnRH antagonist and testosterone, GnRH-induced gonadotrophin secretion was consistently lower compared with that after GnRH antagonist alone (P less than 0.05), but was increased compared with that after testosterone alone (P less than 0.05). Thus, in the presence of a GnRH antagonist the feedback action of testosterone on LH and FSH was diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Stability of spermatogenic synchronization achieved by depletion and restoration of vitamin A in rats.

Studies of synchronization of spermatogenesis following vitamin A deficiency have suggested that this may provide an in vivo model for the study of stage-dependent changes in hormonal action and protein secretion within the seminiferous epithelium. However, until now, no information on the stability or durability of this condition has been available. In this study, 200 seminiferous tubules from each of 40 rats (including controls) were classified according to their spermatogenic stage after withdrawal and replenishment of vitamin A. Following 15 wk withdrawal and subsequent replenishment of vitamin A, spermatogenesis was initiated in a synchronous fashion. This synchrony remained stable for more than 10 cycles of the seminiferous epithelium (2.5 spermatogenic cycles). In association with the extended period of vitamin A deficiency, a proportion of tubules (30%) showed morphological characteristics of either Sertoli cells only or Sertoli cells plus spermatogonia with occasional pachytene spermatocytes. During the 11-wk period of observation in this study, no significant change in proportions of damaged tubules were observed. Testicular testosterone concentrations, although elevated with respect to controls, showed no correlation with the stage of the cycle of the seminiferous epithelium observed, whereas pituitary and serum follicle-stimulating hormone levels were elevated, probably due to the number of damaged tubules observed. The persistence of synchrony in spermatogenesis following vitamin A treatment suggests that this model is applicable for studies of paracrine actions within the testis. However, the decreased ratio of synchrony observed with time may provide evidence that duration of the individual stages of the cycle of the seminiferous epithelium might be subject to temporal variation, leading to a progressive desynchronization of spermatogenesis in this model system.

Animals↗

PubMed1990

Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta).

Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.

Animals↗

PubMed1990

Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats.

The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 micrograms/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3 X 5 cm, sc), dihydrotestosterone-filled Silastic implants (3 X 5 cm, sc), E2 benzoate (15 micrograms/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotestosterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed1990

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates.

The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone-enanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosterone-enanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290 +/- 340 (dihydrotestosterone-enanthate) vs 2920 +/- 485 (testosterone-enanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half-life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys.

Androgens↗

PubMed1989

Fluid-phase transcytosis in the primate epididymis in vitro and in vivo.

Ligated tubules from the corpus epididymidis of men and monkeys were incubated in medium containing horseradish peroxidase (HRP) as a marker for fluid-phase endocytosis. HRP was localized by light and electron microscopy after 0, 15, 30 and 60 min of incubation. Movement between the cells was prevented by tight junctions, but bypass of this barrier was apparently achieved by an intracellular vesicular mechanism leading to a time-dependent appearance of HRP in the lumen. Uptake of HRP into basal cells and capture by the lysosomal apparatus of principal cells were also observed. HRP-filled vesicles also appeared in the basal, mid and apical cytoplasm of epithelial cells in the caput 1 h after injection of the tracer into the epididymal circulation of the monkey, suggesting that this pathway also operates in vivo.

Aged↗

PubMed1989

Testosterone and dihydrotestosterone, but not estradiol, selectively maintain pituitary and serum follicle-stimulating hormone in gonadotropin-releasing hormone antagonist treated male rats.

Recently it has been found that testosterone can maintain and restimulate serum and pituitary follicle-stimulating hormone (FSH) in the gonadotropin-releasing hormone (GnRH) antagonist treated adult male rat. The present investigation was undertaken to determine (1) which metabolite of testosterone, dihydrotestosterone (DHT), or estradiol accounts for the effects of testosterone in GnRH antagonist suppressed rats and (2) whether these effects of testosterone are influenced by other testicular factors. Eight groups of 6-8 adult male Sprague-Dawley rats were subjected to the following treatments: vehicle, GnRH antagonist (75 micrograms/day s.c.), testosterone-filled Silastic implants (3 x 5 cm, s.c.), DHT-filled Silastic implants (3 x 5 cm, s.c.), estradiol benzoate (15 micrograms/day s.c.), and combined administration of GnRH antagonist with either steroid. In addition, the GnRH antagonist/testosterone treatment regimen was applied to rats orchidectomized 72 h prior to initiation of treatments. After 3 weeks of treatment, serum was analyzed for concentrations of luteinizing-hormone (LH), FSH, testosterone, DHT, and estradiol. Pituitary extracts were analyzed for LH and FSH content. Except for the vehicle-treated groups, serum and pituitary LH concentrations were markedly suppressed by all treatments. In intact rats treated with GnRH antagonist alone and/or estradiol, the pituitary FSH level was reduced by more than 70% relative to controls, while both testosterone and DHT maintained pituitary FSH. Similarly, testosterone and DHT, but not estradiol, delayed the decline of serum FSH induced with GnRH antagonist alone. In orchidectomized animals, testosterone was also capable of preventing a reduction of pituitary FSH despite concomitant GnRH antagonist administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Evidence for a major role of inhibin in the feedback control of FSH in the male rat.

Adult rats (16-18/group) received a single intratesticular injection of 25, 100 or 400 microliters glycerol solution (7:3 in distilled water, v/v). Half of the rats in each group were given implants of testosterone, a testosterone-filled Silastic capsule (1.5 cm length) to provide serum values of testosterone within the normal range. After 1 week all animals were killed by decapitation. Serum concentrations of gonadotrophins, testosterone and immunoactive inhibin as well as testicular concentrations of testosterone and bioactive inhibin were determined. Testicular histology was studied in Paraplast-embedded tissue stained with PAS and haematoxylin-eosin. Glycerol treatment caused a dose-dependent ablation of spermatogenesis in a distinct area around the site of injection. Serum concentrations of FSH increased proportionally with increasing spermatogenic damage while serum LH and testosterone remained unaltered except with the highest glycerol dose. The rise in serum FSH was significantly correlated with serum (r = -0.70, P less than 0.001) and testicular (r = -0.66, P less than 0.001) concentrations of inhibin. A less pronounced correlation was found between LH and serum inhibin (r = 0.48). No correlation was found between the concentrations of LH and testicular inhibin or between serum concentrations of FSH and serum testosterone in the 25 and 100 microliters groups. Maintenance of low to normal serum testosterone concentrations by means of Silastic implants blocked the elevation of FSH in glycerol-treated animals but failed to affect significantly serum FSH in untreated rats. In all testosterone treated rats testicular inhibin concentrations were markedly reduced in the presence of lowered concentrations (7-14%) of testicular testosterone and unaltered serum FSH concentrations.

Animals↗

PubMed1989

Differential effects of FSH and testosterone on the maintenance of spermatogenesis in the adult hypophysectomized rat.

In order to clarify further the role of FSH in the maintenance of spermatogenesis, adult rats were treated with purified human FSH (2 X 5 IU/day per rat), testosterone (1.5 cm silicone elastomer implant) or a combination of both hormones for 2 weeks following hypophysectomy. After hypophysectomy alone, no elongate spermatids were observed and the numbers of pachytene spermatocytes and round spermatids observed were reduced when compared with untreated controls. Testosterone supplementation alone qualitatively maintained the formation of elongate spermatids in most seminiferous tubules, whilst in FSH-treated rats increased numbers of round spermatids and pachytene spermatocytes were observed when compared with hypophysectomized animals. Formation of elongate spermatids, however, did not occur under FSH treatment alone. A combination of FSH and testosterone treatment maintained spermatogenesis in an almost quantitative fashion. Numbers of pachytene spermatocytes and round spermatids were maintained at about 80% of levels seen in intact control animals. Treatment with FSH or testosterone alone maintained testis weights at significantly higher levels than those seen in hypophysectomized controls (FSH, 0.79 +/- 0.05 g; testosterone, 0.81 +/- 0.07 g; hypophysectomized, 0.50 +/- 0.04 g). Animals treated with FSH and testosterone showed testis weights 20% below control values (1.22 +/- 0.05 vs 1.51 +/- 0.06 g; P less than 0.05). No increases in intratesticular or intratubular androgen concentrations or in testosterone: dihydrotestosterone ratios were observed in any of the hormone-treated groups when compared with hypophysectomized controls. In all hypophysectomized animals testicular androgen concentrations were reduced to less than 5% of control values. The results obtained in this study suggest that FSH is involved in the maintenance of spermatogenesis in the adult rat and that the effects of FSH are not mediated through changes in intratesticular androgens. Low levels of testosterone in combination with FSH can almost quantitatively maintain spermatogenesis in adult rats.

Androgens↗

PubMed1989

Radioimmunoassay of inhibin in the serum of male monkeys.

A heterologous inhibin radioimmunoassay method to measure inhibin in serum of male cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys has been validated using a specific antibody against bovine 31 kDa inhibin and 125I-labelled 31 kDa inhibin as tracer. A serum pool from male monkeys was used as standard. Serial dilutions of normal monkey serum showed parallel logit-log dose-response curves to purified porcine and bovine inhibin as well as to a female human serum pool. The intra-assay coefficient of variation was 4.2% (n = 10) and the interassay coefficient of variation 5.1% (n = 10). No loss of inhibin immunoactivity was noted after storage at 23 degrees C for 5 days or repeated thawing and freezing of the serum samples. Serum from castrated monkeys showed undetectable levels of inhibin. Treatment with a gonadotrophin-releasing hormone agonist for 15 weeks led to a marked suppression of peripheral serum inhibin to concentrations similar to those after hypophysectomy or pituitary stalk section.

Animals↗

PubMed1989

Sustained inhibition of sperm production and inhibin secretion induced by a gonadotrophin-releasing hormone antagonist and delayed testosterone substitution in non-human primates (Macaca fascicularis).

Since the concomitant administration of a gonadotrophin-releasing hormone (GnRH) antagonist and testosterone suppresses sperm production only incompletely, the feasibility of treatment with a GnRH antagonist and delayed testosterone supplementation for sustained suppression of sperm production in a non-human primate model was investigated. Adult cynomolgus monkeys (Macaca fascicularis; five/group) received daily s.c. injections of the GnRH antagonist [N-acetyl-D-2-naphthyl-Ala1,D-4-chloro-Phe2, D-pyridyl-Ala3,nicotinyl-Lys5,D-nicotinyl-Lys6, isopropyl-Lys8,D-Ala10]-GnRH of either 450 or 900 micrograms/kg for 18 weeks. During week 6 of the GnRH antagonist treatment, all monkeys were given a single i.m. injection of 40 mg of a long-acting testosterone ester (testosterone-trans-4-n-butylcyclo-hexanecarboxylate; 20-Aet-1). Within 1 week, serum LH bioactivity was suppressed in both groups and remained low throughout the entire treatment period. Similarly, concentrations of serum testosterone declined precipitously. During week 6, substitution with testosterone restored concentrations of serum testosterone into the pretreatment range. Concentrations of serum inhibin declined within 1 week and remained suppressed during the period of treatment with the GnRH antagonist. Testicular volumes were reduced to approximately 25% of pretreatment values in both groups by week 8 and stayed in that range during the remaining period of administration of the GnRH antagonist. During the first 6 weeks of administration of the GnRH antagonist, the ejaculatory response to electrostimulation and the volume of the ejaculates diminished with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Quantitative analysis of germ cell numbers and relation to intratesticular testosterone following vitamin A-induced synchronization of spermatogenesis in the rat.

Synchronization of spermatogenesis would provide an ideal model for the investigation of stage-dependent changes in the secretion of paracrine factors. In vitamin A-deficient animals subsequently injected with vitamin A, over 80% of seminiferous tubules were synchronized within three to five stages of the seminiferous cycle. Following replenishment of vitamin A, spermatogenic stages IV-VI (35 days), VI-VIII (38 days), IX-XII (41 days), I-IV (45 days) and V-VII (48 days) were observed. Despite synchronization of spermatogenesis at all stages, spermatogenesis was markedly impaired when evaluated in a quantitative fashion. At all times evaluated, numbers of round spermatids were reduced compared with age-matched controls. Numbers of pachytene spermatocytes reached control values only after 45 days of vitamin A replenishment. Elongate spermatids were almost totally absent up to 41 days after vitamin A replenishment. Testicular and epididymal weights were also reduced, although testicular weights showed a significant recovery over the time-course of the study. Serum and pituitary concentrations of LH and FSH were raised at the commencement of the study, with serum gonadotrophins returning to control values 48 days after vitamin A replenishment. Both testicular and serum testosterone concentrations in treated animals tended to be higher than in the controls. Although synchronization of spermatogenesis was achieved, testicular testosterone concentrations did not reflect the stage-dependent cyclical changes observed in earlier studies. Testicular concentrations of testosterone were raised throughout the period of observation with the exception of animals synchronized around stages II-IV of the spermatogenic cycle. No correlation between the most frequent stages and intratesticular testosterone was found (r = 0.06, P greater than 0.1). Previous observations that testosterone concentrations are selectively increased at stages VII-VIII of the spermatogenic cycle are not supported by the present study.

Animals↗

PubMed1989

Reversibility of GnRH agonist-induced inhibition of testicular function: differences between rats and primates.

In rats, GnRH agonists can induce focal and permanent testicular damage. No such effects have been found in dogs, monkeys and volunteers participating in contraceptive trials. Some of the severe alterations observed in prostatic cancer patients treated with GnRH agonists might be influenced by age and/or disease status. To date no irreversible testicular damage in human and non-human primates, clearly attributable to GnRH agonist treatment has been described. In consequence, the rat appears an unsuitable model for evaluation of the antitesticular effects of GnRH agonists in primates. Thus, non-human primates play an important role in the preclinical evaluation of GnRH analogues.

Animals↗

PubMed1989

Movement characteristics of ejaculated sperm from cynomolgus monkeys (Macaca fascicularis) analyzed by manual and automated computerized image analysis.

Sperm motility is an important indicator of male reproductive function. An automated computerized system was used to measure the movement characteristics of cynomolgus monkey sperm. Swimming velocities were in good agreement with data derived from tracking sperm heads manually with a digitizer, but sperm counting by the system was erroneous. In some ejaculates, there were two subpopulations of sperm with different curvilinear velocities, linearities of swim-paths, and lateral movements of the heads.

Animals↗

PubMed1988

Testosterone prevents complete suppression of spermatogenesis in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis).

We studied the effects of administration of a GnRH antagonist combined with testosterone (T) as an approach to male contraception as well as the role of intratesticular androgens in spermatogenesis using a nonhuman primate model. Three groups of five adult cynomolgus monkeys (Macaca fascicularis) received daily sc injections of 420-460 micrograms/kg GnRH antagonist ([Ac-D2Nal1,D4ClPhe2,DPal3,Arg5,DGlu6(AA), DALa10]GnRH) for a period of 15 weeks. T supplementation, commencing on the first day of GnRH antagonist administration, was provided by single im injection of 40 mg (group 2) or 200 mg (group 3) of the long-acting testosterone ester testosterone-trans-4-n-butylcyclohexancarboxylate (20-Aet-1). Serum LH bioactivity was undetectable within 1 week of GnRH antagonist administration in all monkeys. GnRH antagonist administration alone (group 1) reduced serum T levels into the castrate range. Forty milligrams of 20-Aet-1 maintained serum T levels in the upper range of normal monkeys, while 200 mg 20-Aet-1 maintained serum T levels about 1.5-fold above normal. The response to electroejaculation was fully maintained in all T-treated monkeys. Sperm counts in the ejaculates dropped to zero among group 1 animals within 7-10 weeks of GnRH antagonist administration. In groups 2 and 3 consistent azoospermia could not be induced, and the sperm counts were significantly (P less than 0.05) higher in group 3 than in group 2. Histologically, spermatogenesis in group 1 was arrested at the spermatogonial level in 75% of seminiferous tubules. In group 2, spermatogenesis proceeded to spermatocytes in 50% of tubules and to elongated spermatids in 10% of tubules, while in group 3 elongation of spermatids occurred in 75% of tubules. The mean T and dihydrotestosterone concentrations in baseline testicular biopsies (n = 15) were 43.8 +/- 6.8 (+/- SE) and 5.7 +/- 1.5 ng/g, respectively. After GnRH antagonist with or without T administration, the mean (n = 15) intratesticular T and dihydrotestosterone levels were reduced to 20.3 +/- 4.9 and 3.2 +/- 0.5 ng/g, respectively, and differed little among the three groups. No correlation, however, could be established between testicular androgen levels and spermatogenic status (P greater than 0.30) or sperm counts (P greater than 0.60). These results demonstrate that administration of a GnRH antagonist in the presence of constant serum T levels does not induce consistent azoospermia, and that the supporting effects of T on spermatogenesis cannot be explained exclusively on the basis of the testicular androgen concentrations.

Androgens↗

PubMed1987

Suppression of spermatogenesis in a nonhuman primate (Macaca fascicularis) by concomitant gonadotropin-releasing hormone antagonist and testosterone treatment.

The effects of concomitant testosterone (T)-supplementation on gonadotropin-releasing hormone (GnRH) antagonist-induced testicular regression in cynomolgus monkeys (M. fascicularis) were investigated. Four adult monkeys were infused via osmotic minipumps with daily amounts of 2 mg of a potent GnRH antagonist (N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) for a period of 104 days. Androgen substitution was provided via T-filled Silastic capsules implanted at initiation of GnRH antagonist treatment. Within 1-4 days of GnRH antagonist administration, serum concentrations of bioactive LH became undetectable. The implants maintained serum T at 50-80% of pre-treatment levels. Sperm production decreased in three out of four monkeys. One animal became azoospermic by the 13th week of treatment and the ejaculates of two other monkeys contained less than 5 X 10(6) sperm. In the fourth monkey, spermatogenesis was less affected. Testicular histology, judging from biopsies at termination of GnRH antagonist treatment, was typical of the hypogonadotropic status in 3 of the 4 monkeys. The most affected tubules contained only spermatogonia and Sertoli cells. Although comparison with GnRH antagonist treatment alone in a previous study indicated a delay of spermatogenic inhibition with testosterone, the present study confirms the potential of GnRH antagonist for male fertility regulation.

Animals↗

PubMed1987

Intratesticular injection of glycerol as a model for studying the quantitative relationship between spermatogenic damage and serum FSH.

Intratesticular injection of glycerol (1,2,3-trihydroxypropane) was evaluated as an experimental approach for studying the relationship between spermatogenic activity, i.e. relative proportion of euspermatogenic and aspermatogenic tubules in the testis, and serum concentrations of FSH. Adult rats received a single intratesticular injection of either 400 microliters distilled water or five different doses of glycerol, ranging from 25 to 400 microliters, and were killed after 1 or 4 weeks respectively. Injection of glycerol caused focal destruction, so that the same testes contained intact tubules, tubules with spermatogonia and Sertoli cells only, and tubules devoid of cellular material. There was a close correlation (r = 0.896) between the frequency of intact tubules and the dose of glycerol, and a similarly strong correlation (r = 0.908) between acellular tubules and the dose of glycerol. A correlation existed between FSH and euspermatogenic tubules (r = -0.758, n = 122) and, conversely, between FSH and acellular tubules (r = 0.820, n = 122), while the correlation for tubules containing spermatogonia and Sertoli cells was only marginal (r = -0.055). The exact relationship between FSH and spermatogenic activity in the testis was used to estimate the minimal amount of spermatogenic tissue necessary for maintaining normal serum concentrations of FSH. Only the disruption of spermatogenesis in more than 30% of seminiferous tubules in each testis caused increased serum concentrations of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗