Biomedical subjects

G F Weinbauer

Publications and source records attributed to G F Weinbauer.

At least 55 records · Page 3Linked to original sources

PubMed1997

Epididymal maturation of chromatin in spermatozoa from control monkeys (Macaca fascicularis) and those treated with Cetrorelix, a gonadotropin-releasing hormone antagonist.

In order to examine changes in sperm chromatin upon epididymal maturation in the macaque epididymis (Macaca fascicularis), spermatozoa were obtained from six regions of the duct and examined for the state of their chromatin condensation by flow cytometry after staining with acridine orange. To see whether changes were affected by androgens, tissue was obtained from five monkeys treated with the gonadotropin releasing hormone (GnRH) antagonist Cetrorelix. Spermatozoa were recovered from treated and control animals after 16 days (at hemicastration) and another 9 days of treatment. Chromatin condensation of epididymal spermatozoa from controls displayed an increase upon maturation. After 16 days of GnRH-antagonist treatment, spermatozoa in the caput epididymidis displayed greater fluorescence than those from controls, but this was reduced during epididymal transit to values found in the distal epididymal regions of the controls. It is concluded that epididymal chromatin condensation 1) is normal in GnRH-antagonist-treated monkeys as long as sperm are being produced and 2) can compensate for poor testis function so that spermatozoa with normal states of chromatin condensation are found in the distal cauda epididymidis and probably the ejaculate.

Animals↗

PubMed1997

Expression of mitotic cyclin B1 is not confined to proliferating cells in the rat testis.

Spermatogenesis is a precisely controlled and timed process comprising mitotic divisions of spermatogonia, meiotic divisions of spermatocytes, and the maturation and differentiation of haploid spermatids. Cell proliferation is controlled by genes involved in the regulation of the cell cycle. Among the principal regulatory proteins are cyclins, which are categorized according to their appearance during the cell cycle. B-type cyclins are mitotic cyclins and function at the G2/M transition of the cell cycle. We have investigated the expression and regulation of cyclin B1 during rat spermatogenesis. Rat cyclin B1 was isolated from a testis cDNA library and further used as a probe to detect mRNA expression. Northern blot hybridization of testis mRNA revealed the presence of a single 1.7-kilobase transcript. In situ hybridization showed stage-specific expression during spermatogenesis with highest expression found in late pachytene spermatocytes and early round spermatids. This pattern was confirmed in fractions of isolated germ cells. Immunocytochemistry displayed highest protein levels in round spermatids. Depletion of gonadotropins did not change the quantitative and qualitative expression pattern of cyclin B1. Therefore, the signals triggering the onset of cyclin B1 expression seem not to originate from the pituitary-gonadal endocrine axis and might therefore be paracrine factors originating within the germinal epithelium. Our observations suggest that cyclin B1 plays a hitherto unknown role in spermatid maturation in addition to its known function in dividing cells.

Amino Acid Sequence↗

PubMed1997

The cynomolgus monkey prostate under physiological and hypogonadal conditions: an ultrasonographic study.

PURPOSE: Although the prostate of the cynomolgus monkey has been shown to be a particularly suitable model for the human, in vivo data on this organ are hardly available. We therefore applied transrectal ultrasonography to the investigation of the physiology and pathophysiology of monkey prostate under normogonadotropic and hypogonadal conditions in vivo. MATERIALS AND METHODS: Five intact and 7 long-term castrated monkeys were analysed repeatedly for assessment of the feasibility and variability of the method. In addition, cross-sectional evaluation was performed on 30 intact monkeys of various ages and on 7 long-term castrated monkeys. Finally, the vehicle (n = 5) controlled effects of androgen deprivation treatment with the GnRH antagonist cetrorelix (n = 4) for 25 days followed by semicastration at day 16 and full castration on day 25 were examined and prostate size was followed thereafter. RESULTS: The monkey prostate shows an ellipsoid shape and ultrasonic appearance similar to the human prostate. Variability in 5 intact monkeys (mean +/- SE = 4.67 +/- 0.55 ml.) and 7 long-term castrated monkeys (0.88 +/- 0.08 ml.) was 8.5% and 5.6% respectively. In intact animals a linear correlation between age and prostate size/animal surface area was found (p = 0.0001). Prostate size in castrated animals was reduced (p < 0.001) compared to intact animals. In the experimental study, GnRH antagonist led to a significant reduction of prostate volume and testosterone levels compared to the vehicle group, while semicastration had no influence. Following removal of the second testis a further decrease of prostate volume was seen (p < 0.0001). When compared, castration and GnRH antagonist treatment induced a similar decrease of prostate volume over time. CONCLUSION: Transrectal ultrasonography provides a feasible and reproducible approach for determination of prostate size in cynomolgus monkeys. Castration and GnRH antagonist treatment are equally effective in reducing prostate size.

Animals↗

PubMed1996

Severe impairment of spermatogenesis in mice lacking the CREM gene.

Spermatogenesis is a complex developmental process that occurs in several phases. A large number of genes have been identified that are expressed during spermatogenesis, but the biological significance of many of these is not yet known. We have used gene targeting to selectively eliminate the transcription factor CREM (cyclic AMP- responsive element modulator), which is thought to be important for mammalian spermatogenesis. Male mice deficient for all CREM proteins are sterile, as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.

Androgens↗

PubMed1996

Maturation of sperm motility in the epididymis of the common marmoset (Callithrix jacchus) and the cynomolgus monkey (Macaca fascicularis).

The acquisition by spermatozoa of the capacity for movement upon liberation from the epididymal duct into buffer is one of the obvious changes associated with sperm maturation and, hence, studies of sperm kinematics might provide good indices for sperm maturation. Profiles of development in the movement pattern of spermatozoa taken from six regions of the epididymis were established in marmoset and cynomolgus monkeys using computer-assisted sperm analysis. Motion of spermatozoa from initial regions was sluggish and irregular, then developed in the more distal region into erratic movement effected by an increase in the vigour of flagellation as reflected by curvilinear velocity. The tendency of immature spermatozoa to display circular motion was more common in the marmoset than in the cynomolgus monkey. In the marmoset the most drastic changes in percentage motility and kinematic parameters of spermatozoa occurred between the distal caput and the proximal corpus; maximal values for these parameters were found around the distal corpus epididymis. For the cynomolgus spermatozoa the sharpest gain in percentage motility was also achieved between the caput and proximal corpus epididymis, but with full kinematic development in the proximal cauda epididymis. These maturational changes were not synchronous among spermatozoa from the same site as they moved along the epididymis, as reflected in the heterogeneity of each sample in the kinematic properties of individual spermatozoa, especially those from the proximal corpus epididymis. The maturational profiles in the monkeys are comparable to the situation in the human, for which they may provide a useful model.

Animals↗

PubMed1995

Gonadotrophin control of testicular germ cell development.

Successful and complete male germ cell development is dependent on the balanced, endocrine interplay of the hypothalamus, the pituitary and the testis. The hypothalamus secretes gonadotrophin-releasing hormone in a pulsatile manner which, in turn, elicits the pulsatile release of the gonadotrophins LH and FSH from the pituitary. Luteinizing hormone stimulates spermatogenesis indirectly via testosterone, whereas FSH acts directly on the seminiferous tubules. The synthesis and release of gonadotrophic hormones is under the feedback control of testosterone. Whether other testicular peptides such as inhibin and activin are also involved is not yet clear. Luteinizing hormone/testosterone and FSH are the prime regulators of germ cell development. On their own, these hormones are capable of exerting clear-cut stimulatory effects on the spermatogenic process. However, the quantitative production of spermatozoa generally requires the presence of both LH/testosterone and FSH. Since receptors for androgens and FSH are confined to the somatic cells of the testis, the trophic effects of these hormones on germ cells must be indirect. However, it is not known as yet precisely which genes/factors mediate the beneficial effects of androgens and FSH on spermatogenesis. The gonadotrophic hormones have been found in a number of isoforms and multiple transcripts of the LH and FSH receptor have been detected. Therefore, the possibility must be considered that certain forms of male infertility could be due to dysfunctional hormones and/or mutated receptors.

Animals↗

PubMed1995

Ubiquitous expression of the androgen receptor and testis-specific expression of the FSH receptor in the cynomolgus monkey (Macaca fascicularis) revealed by a ribonuclease protection assay.

Androgens are known to exert a variety of effects on an organism while follicle-stimulating hormone (FSH) seems to act specifically on the gonads. To investigate whether these effects are reflected by the expression pattern of the androgen receptor (AR) or the FSH receptor (FSHR) we screened 38 different tissues and organs of one intact and one castrated male non-human primate (Macaca fascicularis). By means of a highly sensitive ribonuclease protection assay (RPA) we demonstrated AR mRNA expression in all tissues of the intact monkey investigated. Immunohistochemistry of selected organs from this monkey revealed a good correlation between AR mRNA and protein expression. In the castrated monkey, the overall AR mRNA expression was markedly lower compared with the intact monkey, although higher expression was present in the pituitary, thyroid and prostate glands. FSHR mRNA was only detected in testicular tissue. This study has revealed, for the first time, ubiquitious expression of the AR mRNA in a non-human primate. The testis-specific expression of the FSHR highlights the importance of FSH for spermatogenesis with the testis being apparently the only target organ.

Animals↗

PubMed1995

Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate.

Testosterone preparations producing constant physiological testosterone serum levels are desirable for long-term treatment of androgen deficiency. However, all injectable testosterone esters used clinically for substitution of male hypogonadism are characterized by unfavourable pharmacokinetics. We therefore tested two groups of five long-term orchidectomized cynomolgus monkeys (Macaca fascicularis), which received a single intramuscular injection of 10 mg/kg body weight of an injectable testosterone undecanoate (TU) preparation or testosterone enanthate (TE) in a preclinical study to assess the pharmacokinetic and pharmacodynamic characteristics of TU in comparison to TE. The dose was equivalent to 6.3 and 7.2 mg of pure testosterone per kilogram body weight in the TU and TE group, respectively. Following injection of TU, mean serum testosterone rose to 58 +/- 18 nmol/l on day 1 and remained at moderately supraphysiological levels of 40-68 nmol/l for 45 days. Thereafter, testosterone levels were maintained in the normal range of intact monkeys for another 56 days. The TE injection resulted in highly supraphysiological levels of 100-177 nmol/l from immediately after the injection to day 5. A rapid decline followed and testosterone levels reached the lower limit of normal after 31 days. Serum testosterone levels were significantly higher in the TE-than in the TU-treated animals on days 0.5-7 (p < 0.05). Significantly lower testosterone levels were seen in the TE than in the TU group on days 16, 22, 25 and 31 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Endocrine control of testicular somatic and premeiotic germ cell development in the immature testis of the primate Macaca mulatta.

Four groups(N = 3 per group) of juvenile rhesus monkeys (Macaca mulatta, 14-20 months old) received either vehicle or highly purified human follicle-stimulating hormone (FSH; 10 IU kg-1 day-1), human chorionic gonadotropin (hCG; 250 IU every alternate day) or both hormones for a period of 4 weeks. Testicular volume and weight increased more than twofold after single and more than sixfold after combined hormone treatment. Serum and intratesticular testosterone were at supraphysiological levels in hCG-treated animals and rose even more after combined treatment; a minor elevation of intratesticular testosterone was also observed after FSH treatment. Serum inhibin was elevated after hCG or FSH treatment and increased more than twofold during the first 3 weeks of combined treatment. Semiquantitative analysis of cell numbers showed a statistically non-significant increase in Sertoli cells and Ad- and Ap-spermatogonia after single hormone treatment. Combined treatment induced a further increase in the number of spermatogonia. Leydig cells were only encountered after hCG treatment; their number was more than threefold higher after combined treatment compared with hCG alone. Follicle-stimulating hormone stimulated Sertoli cell and Ap spermatogonia proliferation but did not induce morphological differentiation of Sertoli cells, peritubular cells or Leydig cells. Human CG treatment, however, induced Sertoli cell proliferation and morphological differentiation. It had effects on spermatogonial proliferation but induced differentiation of peritubular cells. Combined treatment initiated the greatest morphological and functional differentiation of Sertoli cells, peritubular cells, Leydig cells and spermatogonia. Flow cytometric analysis confirms an increase of mitotically active cells. The observations show that FSH and testosterone can induce Sertoli cell proliferation. Morphological differentiation of Sertoli cells may be mediated indirectly by environmental and paracrine stimuli released from peritubular cells, whose differentiation is androgen dependent. Leydig cells are stimulated mainly by hCG. Our present and previous data lead us to propose that FSH contributes to the final number and activity of Leydig cells, which secrete immunoreactive inhibin in response to hCG.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed1995

Identification of male germ cells undergoing apoptosis in adult rats.

The possible role of apoptosis in spontaneous or induced germ cell death was investigated by treating adult male rats with either a GnRH antagonist (112.5 micrograms kg-1 day-1 for 14 days) or methoxyacetic acid (650 micrograms kg-1; single dose) or sham-treated with either of the vehicles (n = 3 per group). The antagonist virtually abolished gonadotrophin secretion, while methoxyacetic acid reduced serum testosterone concentrations and slightly increased those of FSH (neither significantly). Bands of low molecular mass characteristic of apoptotically degraded DNA were detected by electrophoresis in both treatment groups but not in the controls. Sectioned, Carnoy-fixed testes were screened for degenerating cells with periodic acid-Schiff's base and haemalaun or examined for apoptotic cells using a modified in situ end-labelling procedure. Periodic acid-Schiff's-stained dying cells were found in low numbers in control animals with a distribution and frequency that matched that of apoptotic cells. Degenerating germ cells identified by histology were present at certain stages of spermatogenesis after 2 weeks of antagonist treatment. A comparison of their distribution with that of end-labelled cells identified the cell death as apoptotic. Methoxyacetic acid caused a massive depletion of spermatocytes at stages IX-II, which was also found to be apoptotic. It is concluded that spontaneous germ cell death in adult rats is apoptotic and that both gonadotrophin ablation and administration of methoxyacetic acid can cause apoptosis in the germ cells of adult male rats, but via different routes.

Acetates↗

PubMed1994

In vitro Sertoli cell bioassay of follicle-stimulating hormone (FSH)-serum from different animal species alters the morphology of rat Sertoli cells without affecting their response to FSH.

Follicle-stimulating hormone (FSH) stimulates aromatase activity of immature rat Sertoli cells cultured in vitro in the presence of an androgen substrate, a phenomenon that can be used to measure FSH bioactivity. This paper analyzes the effects of sera from various animal species on both aromatase activity and morphological aspects of cultured rat Sertoli cells. Treatment of Sertoli cells with increasing concentrations of serum from humans, monkeys, rats, hamsters, and mice gave a dose-dependent stimulation of estradiol production parallel to the response obtained with FSH standard. Serum from these species and from rabbits also had a characteristic morphological effect on the cells, to produce a fibroblast-like aspect and clumping. This effect was dose-dependent, was increased by the addition of FSH, and was eliminated by heating the sera at 56 degrees for 30 min prior to incubation with the cells. Clumping did not interfere with the aromatase activity of Sertoli cells and did not cause the cellular response to deviate from parallelism with the standard curve. Heat treatment of FSH standard and serum samples did not significantly change the aromatase activity. FSH bioactivity could be measured accurately in intact and castrated monkeys. It is concluded that the Sertoli cell aromatase bioassay can be applied directly to the measurement of serum bioactive FSH in several animal species without any preliminary treatment of the serum samples.

Animals↗

PubMed1994

The effect of androgens and antiandrogens on the immunohistochemical localization of the androgen receptor in accessory reproductive organs of male rats.

The androgen receptor (AR) was localized immunohistochemically after different hormonal treatments in the ventral prostate, coagulating gland, seminal vesicle and epididymis of the adult rat. In the untreated controls AR-immunoreactivity was confined to the cell nuclei. One week after castration or treatment with the gonadotropin-releasing hormone antagonist Cetrorelix (150 micrograms/animal per day) a cytoplasmic staining occurred in the epithelial cells of the ventral prostate and in part of the coagulating gland and seminal vesicle. In contrast, the AR remained exclusively in the nuclei in the epididymal epithelium and the glandular smooth muscle layer even after 2 weeks of androgen depletion. Bolus injections of either dihydrotestosterone (1 mg/kg), the antiandrogen flutamide (40 mg/kg), or the novel non-steroidal antiandrogen casodex (40 mg/kg) to androgen-depleted animals eliminated cytoplasmic AR-immunoreactivity and restored the nuclear staining pattern in the ventral prostate. A sustained 2-week treatment with the antiandrogens resulted in a loss of weight in all organs but did not alter the distribution of AR-immunoreactivity. The data show an apparent cytoplasmic/nuclear ligand-dependent translocation of the AR in the ventral prostate, coagulating gland and seminal vesicle but not in the epididymis of the adult rat.

Amino Acid Sequence↗

PubMed1994

Immunohistochemical localization of proliferating cell nuclear antigen as a tool to study cell proliferation in rodent and primate testes.

The immunohistochemical localization of proliferating cell nuclear antigen (PCNA) has become a widely used method for the detection of proliferating cells in cancerous tissues. PCNA expression is maximal around the S phase of the cell cycle. This study has evaluated the applicability of PCNA localization for the analysis of germ cell proliferation in rats, Djungarian hamsters, rhesus and cynomolgus monkeys and men, using Bouin's-fixed, paraplast-embedded tissue. In addition, involuted testes from photoinhibited hamsters, testes from immature rhesus monkeys and from GnRH antagonist-treated rats and cynomolgus monkeys were included. Monoclonal mouse anti-PCNA antibody (clone: PC10) was used for detection of the antigen. Visualization was performed by immunogold-silver staining or avidin-biotin staining. PCNA labelling was confined to the nuclei of spermatogonia and early spermatocytes within the seminiferous epithelium of all species. The distribution of PCNA among the different types of A-spermatogonia in primates is in good agreement with the previously described proliferation pattern of these cells. No staining was observed in resting A-dark spermatogonia, while differentiating A-pale spermatogonia were positive at distinct stages of the seminiferous epithelium cycle. In the rodent species the pattern of labelled A-spermatogonia was stage-specific, but agreed only partly with the previously described pattern of mitotic figures of A-spermatogonia. Hormonal withdrawal induced a decrease in the number of PCNA-positive cells in adult rats, hamsters and monkeys. In immature testes from rhesus monkeys positive staining was present in spermatogonia but also in some Sertoli cells, indicating proliferative activity of Sertoli cells in the prepubertal stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Duration of the cycle of the seminiferous epithelium, estimated by the 5-bromodeoxyuridine technique, in laboratory and feral rats.

The stability of the duration of the cycle of the seminiferous epithelium was determined by investigating incorporation of 5-bromodeoxyuridine into S-phase germ cells of normal and hemicastrated standard laboratory rats (Sprague-Dawley) and feral Brown/Norway rats (Rattus norvegicus). Feral rats were trapped on farms in the surroundings of Münster. The duration of the cycle of the seminiferous epithelium, determined at intervals of 12 days (3 h versus 12 days 3 h after 5-bromodeoxyuridine injection), was remarkably constant and similar in intact laboratory rats (12.49 +/- 0.05 days, n = 13, mean +/- SEM) and feral rats (12.44 +/- 0.06 days, n = 8). In hemicastrated laboratory and feral rats the duration of the cycle was similar to that in intact animals, indicating that hemicastration did not influence the kinetics of the seminiferous epithelium cycle. However, the coefficients of variation of the estimated duration of the cycle of the seminiferous epithelium were at least three times lower in hemicastrated rats (one testis from the same animal serving as reference point) compared with that of intact rats (the reference point based on the average staining frequency at 3 h). Overall, no significant differences between laboratory and feral rats could be observed with regard to testis weight and serum concentrations of FSH and testosterone. The number of cells per testis, determined by flow cytometry, was similar in laboratory and feral rats, except for a slight but significant difference in the haploid:tetraploid cell ratio (6.3 +/- 0.2 versus 7.5 +/- 0.3, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Pharmacokinetics and pharmacodynamics of recombinant and urinary human FSH in the male monkey (Macaca fascicularis).

A dose-finding study was performed in adult male monkeys (Macaca fascicularis) to evaluate the pharmacokinetics and pharmacodynamics of a recombinant human FSH preparation (rhFSH). Groups of five monkeys were randomly assigned to receive single i.m. injections of 0.9% (w/v) NaCl (diluent), 6, 12 or 24 IU rhFSH/kg or 24 IU urinary human FSH/kg (uhFSH). The doses were based on an in vivo ovarian weight gain assay. Blood samples were collected 24 h before and immediately prior to injections, and 4, 8, 12, 24, 72 and 96 h after injections for determination of serum levels of immunoactive FSH by fluoroimmunoassay, bioactive FSH by an in vitro Sertoli cell assay, and inhibin and testosterone by radioimmunoassay. Inhibin was chosen as a marker for in vivo hFSH activity, since the secretion of inhibin in male monkeys is under the control of FSH. Administration of hFSH resulted in dose-related increases in serum hFSH concentrations. rhFSH and uhFSH exhibited similar pharmacokinetics. Comparable findings were obtained when serum samples were analysed for in vitro FSH bioactivity. Maximum serum hFSH levels were obtained 4-6 h after administration and the elimination half-life of hFSH was on average 18-22 h. The serum pharmacokinetics of rhFSH were linear within the dose range explored. Baseline inhibin concentrations varied significantly between groups. However, when the changes in inhibin concentrations were normalized to the baseline values (per cent change, area under curve and maximum inhibin level), a dose-dependent stimulatory effect of rhFSH on serum inhibin was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Can testosterone alone maintain the gonadotrophin-releasing hormone antagonist-induced suppression of spermatogenesis in the non-human primate?

The combination of gonadotrophin-releasing hormone (GnRH) antagonist and delayed testosterone substitution provides a promising approach towards male contraception. However, the GnRH antagonists used clinically so far cause side-effects and have to be administered continuously. We therefore used the non-human primate model to see whether the GnRH antagonist cetrorelix (which exhibits a favourable benefit-to-risk ratio in terms of anti-gonadotrophic action in normal men) induces complete and reversible suppression of spermatogenesis and whether GnRH antagonist-induced suppression of spermatogenesis can be maintained by testosterone alone. Four groups of adult cynomolgus monkeys (Macaca fascicularis; five per group) were injected daily with 450 micrograms cetrorelix/kg ([N-acetyl-D-2-naphthyl-Ala1, D-4-chloro-Phe2, D-pyridyl-Ala3, D-Cit6, D-Ala10]-GnRH). Group 1 received the GnRH antagonist for 7 weeks followed by vehicle administration for another 11 weeks; group 2 was treated with GnRH antagonist for the entire 18 weeks with each animal receiving a single testosterone implant during weeks 11-18 to restore the ejaculatory response to electrostimulation; group 3 received the GnRH antagonist for 18 weeks and testosterone buciclate (TB) was injected during week 6 of GnRH antagonist treatment; group 4 was subjected to GnRH antagonist administration for 7 weeks and received TB (200 mg/animal) during week 6. Under GnRH antagonist treatment alone serum concentrations of testosterone were suppressed. TB maintained testosterone levels two- to fourfold above baseline levels in groups 3 and 4 and prevented the recovery of LH secretion for about 20 weeks after GnRH antagonist withdrawal, whereas inhibin levels increased significantly from week 8 onwards. Group 2 animals were azoospermic during weeks 12-18 of GnRH antagonist administration. The TB-replaced groups developed azoospermia or became severely oligozoospermic. Quantitation of cell numbers by flow cytometry during weeks 6 and 18 revealed that TB (groups 3 and 4) had prevented a further decline of germ cell production compared with group 2 but had maintained the spermatogenic status present at week 6 (onset of TB substitution). All inhibitory effects of cetrorelix and/or TB were reversible after cessation of treatment. These findings demonstrate that cetrorelix reversibly inhibits spermatogenesis in a non-human primate model. Although TB maintained the GnRH antagonist-induced suppression of spermatogenesis, azoospermia was not achieved. This latter effect may reflect either a direct spermatogenesis-supporting effect of the high dose of TB or the partial recovery of inhibin secretion (indirectly reflecting FSH secretion) or a combination of both.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Localization of inhibin/activin subunits in the testis of adult nonhuman primates and men.

The localization and distribution of inhibin/activin subunits was evaluated in the testes of three nonhuman primate species (Macaca fascicularis, M. mulatta, M. arctoides), of young (31 to 43 years) and old (60 to 85 years) men, and of men with disturbed or arrested spermatogenesis using immunohistochemical techniques (peroxidase-anti-peroxidase and alkaline-phosphatase/anti-alkaline-phosphatase technique). Specific polyclonal (anti-porcine inhibin alpha-1-32 and anti-bovine activin A) and monoclonal (anti-human inhibin alpha-1-32 and anti-human activin beta A-82-114) antisera were employed. Among all nonhuman primate species and in men, inhibin/activin subunits were present in the cytoplasm of Sertoli cells and Leydig cells but not in germ cells. No relationship could be established between the staining pattern for inhibin/activin subunits and the completeness or the stage of the spermatogenic process. The staining for the beta A-subunit in Sertoli cells appeared more intense in the testes of old men compared with that of young men. The majority of Leydig cells contained either the alpha-subunit and beta A-subunit or the beta A-subunit alone. The signal for the beta A-subunit was remarkably intense in normal and hyperplastic human Leydig cells. These observations demonstrate the presence of inhibin/activin subunits in Sertoli cells and Leydig cells of adult primates and raise the possibility that these subunits or their respective dimers (inhibin A/activin A) might subserve a paracrine/autocrine role in the adult primate testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗

PubMed1993

Molecular composition of two different batches of urofollitropin: analysis by immunofluorimetric assay, radioligand receptor assay and in vitro bioassay.

The molecular heterogeneity of two different batches of commercially available urofolitropin was analyzed after fractionation by isoelectric focusing (IEF). FSH was measured before and after IEF by a highly specific time-resolved immunofluorimetric assay (IFMA), by a radioligand receptor assay (RRA) employing a preparation of calf testis FSH receptors, and by the in vitro bioassay based on FSH-dependent aromatase stimulation in immature rat Sertoli cells. An overall good correspondence between the results obtained with the three different methods was observed. However, the RRA and the in vitro bioassay appeared to be more suitable than the IFMA in resolving individual FSH isoforms. The mean isoelectric points of the two FSH preparations analyzed were slightly different, due to different molecular composition. These differences, however, seem too minute to be considered as cause of the different pharmacokinetics of FSH described in the literature or to explain the inconsistent therapeutical results seen in patients treated with FSH of urinary origin.

Animals↗