Search PubMed⌕ Search

Biomedical subjects

A R Sheth

Publications and source records attributed to A R Sheth.

At least 73 records · Page 4Linked to original sources

Biosynthesis and localization of inhibin in human prostate.

Inhibin biosynthesis by human prostatic tissue was investigated in vitro. Serum levels of inhibin as well as tissue concentrations in different cells and zones of the normal and benign hyperplastic prostates were determined. Immunocytochemical localization of inhibin identified the involvement of epithelial but not stromal cells in the synthesis and release of prostatic inhibin into the circulation. The endocrine and paracrine functions of prostatic inhibin remain to be elucidated.

Estradiol↗

Circulating levels of inhibin, prolactin, TSH, LH, and FSH in benign prostatic hypertrophy before and after tumor resection.

Using specific radioimmunoassays, serum prolactin, TSH, LH, FSH, and inhibin levels were estimated in normal subjects and in patients with benign prostatic hyperplasia (BPH) before and after tumor resection. In the case of BPH, there was a significant rise in inhibin levels as compared to age-matched control groups, whereas LH and FSH levels were decreased significantly. The levels of inhibin and prolactin were significantly reduced after surgery, but no consistent changes in LH, FSH, or TSH levels were noted. The changes observed in hormonal levels in the BPH patients were not related to patient's age or size of the tumor.

Aged↗

Antibodies to human seminal plasma inhibin cause sperm agglutination and impairment of cervical mucus penetration and sperm-egg attachment.

Inhibin isolated from human seminal plasma which has 94 amino acids has been shown to be structurally similar to a sperm coating antigen of prostatic origin. Specific antibodies generated against this peptide caused agglutination of human sperm. Using FITC-labeled antibody, antigen was localized on the post-acrosomal head region of sperm. Antiserum to inhibin could also impair the penetration of human spermatozoa into cervical mucus. After 10 and 30 minutes, the depth and density of penetration as well as the motility of the sperm were inhibited. The treatment of sperm with antiserum to inhibin caused an inhibition of sperm attachment to the egg as well as inhibition of penetration.

Cervix Mucus↗

Inhibin-like material--an immunohistologic marker for prostatic origin of metastases.

Immunocytochemical localization of inhibin-like material (ILM) using a specific antiserum generated against ILM of prostatic origin was carried out in metastatic lymph nodes of known primary prostatic tumours and in rectal biopsies showing direct invasion with known prostatic carcinoma. Nine of the 11 metastatic lymph nodes gave positive reaction, which was readily apparent in differentiated tumours showing micro-acinar formation. In poorly differentiated tumours it was often focal and indicated intracytoplasmic staining within randomly scattered cells. Rectal biopsies showing invasion of prostatic carcinoma (4 cases) also showed positive reaction for ILM. Using this experimental protocol, the reaction for metastatic lesions from patients with non-prostatic carcinomas was completely negative indicating the specificity of the test for prostatic origin of metastasis. In conclusion, the present investigation indicates the potential application of ILM in confirming or excluding the prostatic origin of invasive tumour in metastatic lesions.

Humans↗

Effect of inhibin on testosterone metabolism by rat ventral prostate in vitro.

Conversion of radiolabeled testosterone to 5 alpha-dihydrotestosterone (5 alpha-DHT) was determined in the rat ventral prostate in vitro, and the effect of inhibin on this conversion was demonstrated. The data revealed that the reduction of testosterone to 5 alpha-DHT was inhibited in a dose-related manner in the presence of inhibin as compared with the basal reduction. The percentage of testosterone reduced per 10-mg tissue also showed a similar trend. The ratio of radioactive counts for DHT and testosterone was also minimum at the highest dose of inhibin used. Inhibin can thus modulate the conversion of testosterone to 5 alpha-DHT in the rat ventral prostate, and therefore can autocrine-paracrine function can be attributed to the prostate.

5-alpha Reductase Inhibitors↗

Biosynthesis of immunoreactive inhibin-like material (IR-ILM) by rat prostate.

Presence of biologically active inhibin-like material (ILM) in the rat prostate was demonstrated by suppression of in vitro follicle-stimulating hormone release from rat pituitaries, and its in vitro biosynthesis was studied by immunoprecipitation of 3H-leucine incorporated in ILM. In vitro biosynthesis of immunoreactive ILM (IR-ILM) was greater in prostate from castrated as compared to intact rats and it decreased in prostates from castrated rats treated with testosterone. In prostates from estrogen-treated castrated animals, an increase in IR-ILM synthesis was observed. These observations indicated that in addition to the testes prostate could be an additional source of ILM and that IR-ILM synthesis in prostate is modulated by hormones.

Age Factors↗

Involvement of prostate in the regulation of serum levels of FSH, LH, and prolactin in male rats.

Circulatory levels of LH and FSH were measured in serum of male rats (28, 35, 42, 63, 70, 77, and 207 days of age) 7 days following sham operation, castration (C), prostatectomy (P), and castration + prostatectomy (C + P). In C + P rats that were 49, 63, 70, 77, and 207 days of age, the plasma FSH was significantly elevated as compared to the C group. Administration of aqueous prostatic extract restored the circulatory FSH level in C + P animals to that observed in C animals, whereas in C animals FSH levels were suppressed, indicating inhibinlike activity. In rats 49 and 77 days of age, circulatory LH levels were significantly suppressed in C + P animals as compared to the C group. Both castration and prostatectomy alone suppressed circulatory prolactin levels. Administration of prostatic extract to castrated animals restored the prolactin levels to that of the sham-operated control animals. Results of the present study suggest a role of the prostate in feedback regulation of FSH and prolactin.

Animals↗

Ultrastructure of monkey (Macaca radiata) spermatozoa: effect of gossypol in vivo.

The present study examines the ultrastructure of ejaculated spermatoza from bonnet monkey, Macaca radiata under normal conditions, with gossypol treatment and during recovery from such treatment. Monkeys were fed orally with gossypol acetic acid (GAA) for 3 months (4 mg/monkey/5 days a week). Semen samples collected by electro-ejaculation, and the spermatozoa were examined using both light and electron microscopy. The degree of motility was also noted by Kalla et al. Ejaculated spermatoza were immotile 90 days after GAA treatment, but little evidence for any abnormality in the spermatozoa could be seen by light microscopy. Some ultrastructural changes were observed, but not to the extent previously reported in spermatozoa of Macaca fascicularis. After termination of treatment, semen samples were obtained every 5th day until sperm count and motility recovered to the normal level. After 90 days only a small proportion of spermatozoa showed abnormal structure. We conclude that in a subhuman animal model gossypol induced effects on sperm motility and morphology are reversible.

Administration, Oral↗

Potential application of inhibin in male and female contraception.

After a review of investigations into the possible use of inhibin in the regulation of male and female fertility, briefly described and summarized in this article, the authors conclude that, at least in experimental animals, inhibin causes a significant reduction in testicular and epididymal spermatozoa in the male and luteal phase defect in the female. The precise mechanism by which inhibin brings about these effects is not known at present, and its elucidation will greatly help in the more effective use of inhibin.

Animals↗

Interference in primate follicular maturation: an approach with inhibin for female contraception.

Investigations to study the effect of inhibin (purified from sheep ovaries) on the corpus luteum function of five regularly cycling bonnet monkeys were undertaken. The treatment with inhibin administered during the first three days of the cycle led to a delay in the occurrence of preovulatory estradiol peak; a reduction in the secretion of estradiol and progesterone during the cycle (significant in 2/5 cycles) and consistent reduction in the length of the luteal phase. There was no interference in the occurrence of physiological events of the cycle such as selection of dominant follicle, ovulation and corpus luteum formation. These results suggest that inhibin or one of its analogues, administered for a short time at the early part of the cycle, might prove useful as a female contraceptive.

Animals↗

Studies on immunocytochemical localization of inhibin-like material in human prostatic tissue: comparison of its distribution in normal, benign and malignant prostates.

A specific antiserum has been generated against inhibin-like material (ILM) of prostatic origin. Using the immunoperoxidase technique, localization of ILM has been examined in a total of 114 prostates including normal (4 specimens), malignant (46) and hyperplastic (55) tissues. ILM positive immunocytochemical reactions were confined to the cytoplasm and not the nucleus of the prostatic acinar cells in the three categories of prostate, whereas the stroma showed negative reactions. The intensity of positive reactions decreased in the following order: Hyperplasia, incidental and moderately differentiated carcinomas, poorly differentiated carcinomas, whereas metaplasia and granulomatous prostatitis gave negative reactions for ILM. Using this experimental protocol, 200 non-prostatic tissue were found to be completely negative, demonstrating the specificity of the test for prostatic epithelium. These findings indicate a potential use of ILM as a marker of prostatic tissue.

Humans↗

Stimulation of ornithine decarboxylase in the rat prostate by seminal plasma inhibin.

The effect of seminal plasma inhibin on ornithine decarboxylase activity (ODC) in the rat prostate was studied. A single bolus injection of seminal plasma inhibin caused a 3- to 4-fold increase in ODC activity within 2 h whereas testicular ODC was unchanged. The ODC response to seminal plasma inhibin was neutralized by specific antibodies generated against the inhibin preparation. Another peptide, thyroid releasing hormone has no effect on prostatic ODC activity, but it blocked the increase in enzyme activity induced by treatment with seminal plasma inhibin.

Animals↗

beta 2-Inhibin contains the active core of human seminal plasma beta-inhibin: synthesis and bioactivity.

The complete synthesis of the C-terminal 28 residues segment 67-94 of human seminal plasma beta-Inhibin, called beta 2-Inhibin, is reported. The Inhibin-like activity of the native 94 amino acids beta-Inhibin is compared to that of the synthetic replica of beta 2-Inhibin. In all assays used both peptides effectively suppress the FSH release induced by LHRH but have little effect on the LH release. In the mouse both peptides are equipotent on a mole basis. In the rat the synthetic beta 2-Inhibin is 3-10 times more potent than beta-Inhibin. Both peptides are active in rat anterior pituitary primary culture assays where maximum suppression of FSH release induced by LHRH occurs around 300 pmol/ml of beta 2-Inhibin. In contrast, maximum suppression of FSH release in the mouse pituitary assay occurs at 10-15 pmol/ml of either Inhibin.

Amino Acid Sequence↗

Binding characteristics of inhibin in rat ventral prostate.

Homogeneous preparation of human seminal plasma inhibin (molecular weight 13,500) was iodinated with 125I to a specific activity of about 40-45 microCi/micrograms and tested for binding to a rat prostate crude membrane preparation. The binding of inhibin was a saturable process as well as time and temperature dependent. This binding was displaceable in a dose-dependent manner by unlabelled inhibin. Other hormones such as LH, FSH, Prl, and TSH from rat or human origin did not influence the binding of labelled inhibin to rat prostate membrane. Of various age groups of rats studied, the maximum binding was observed in 75-day-old rats. The radiolabelled inhibin also showed specific binding to rat pituitary. The preliminary studies regarding involvement of steroids in the control of inhibin receptors in prostate and pituitary indicated that testosterone activates the inhibin receptors at the prostatic level whereas estradiol did not have any effect. However, estradiol increases the pituitary receptors for inhibin as compared to testosterone.

Activin Receptors↗