Biomedical subjects

A R Sheth

Publications and source records attributed to A R Sheth.

At least 19 recordsLinked to original sources

PubMed1994

Excretory profile of inhibin-like peptide (ILP) during human menstrual cycle: a probable marker for determination of fertile period.

The excretory profile of inhibin-like peptide (10.4 kDa) and its interrelationship with urinary LH, FSH, oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during the menstrual cycle were studied. These hormones/metabolites were estimated in daily early morning urine samples obtained from 20 regularly menstruating women. The data revealed that the excretory profile of inhibin-like peptide (ILP) follows a pattern similar to that of E1G. In 17 cycles, ILP peaked 3-4 days prior to the urinary LH peak. A value of 70 ng/mg creatinine (95th centile of ILP levels obtained between 2 and 4 days prior to urinary LH peak and also 5th centile of peak ILP levels) was considered as an indicator of the start of the fertile period. A value of PdG more than 2 micrograms/mg creatinine on two consecutive days was considered as an end of the fertile period. The entire fertile period could be determined in 18 out 20 cycles when criteria based on ILP and PdG levels were applied (accuracy, 90%), whereas it could be determined in 13 out of 20 cycles when criteria based on E1G and PdG levels were applied (accuracy, 65%). Thus, ILP levels in urine may prove to be one of the signals for determining the start of fertile period.

Adult↗

PubMed1994

Prostate inhibin peptide (PIP) in prostate cancer: a comparative immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.

Acid Phosphatase↗

PubMed1994

Detection of prostatic-inhibin-like peptide in the cytoplasm of LNCaP cells, a human prostatic adenocarcinoma cell line.

Prostatic inhibin peptide (PIP) is a 94-amino acid peptide involved in various cellular functions. The concentration of this peptide changes with prostatic pathophysiology suggesting a role in various disease conditions; present study was undertaken to investigate the presence of this peptide in two human prostatic cell lines: LNCaP and PC3 cells. The LNCaP cells showed an intense intracellular fluorescence pattern after staining with rabbit-anti-PIP antiserum and FITC conjugated goat antirabbit-IgG, while the PC3 cells did not exhibit any fluorescence. There was no alteration in the concentration of PIP in LNCaP cells with or without supplementation of steroids in culture medium. Immunoblot analysis indicates similarities between PIP from LNCaP cells and that from the human seminal plasma. Thus, present study demonstrates the presence of PIP in a human prostatic cell line, i.e., LNCaP cells. Its intracellular concentration is androgen independent, and has a close similarity with PIP isolated from the human seminal plasma.

Adenocarcinoma↗

PubMed1994

Expression of a 10.5 kDa inhibin in the endometrium of bonnet monkey on treatment with an antiprogestin ZK 98.299: an immunocytochemical study.

Immunocytochemical localization of inhibin was carried out in paraffin embedded tissue sections of the control and antiprogestin (ZK 98.299)-treated bonnet monkey endometrium using polyclonal antibodies generated against human seminal plasma inhibin (10.5 kDa). The study shows that administration of low doses (5 mg/week) of antiprogestin results in an increase in the expression of inhibin by the endometrium. Treatment with higher doses (20 mg/week) caused a decrease in the expression. Since treatment with higher doses also caused atropic changes in the endometrium, the decrease in inhibin could be the result of morphological damage to the endometrium rather than the effects of antiprogestin on the expression of inhibin. The potential involvement of endometrial inhibin in the process of nidation is speculated.

Animals↗

PubMed1994

Mesoderm enhancing effect of human seminal plasma inhibin and its synthetic C-terminal nonapeptide fragment in the chick embryo.

Isomers of fibroblast growth factor and members of the transforming growth factor beta family have been identified as potent mesoderm inducing factors, particularly in amphibians. Activins belonging to the latter group are capable of inducing all types of mesoderm. Inhibins, also belonging to the same family of proteins have an exactly opposite biological action than activins in the adult organism. We have examined the effects of human seminal plasma inhibin on the early development of the chick embryo, where also activins appear to be important in mesoderm induction. Contrary to expectations, inhibin brought about stimulation of development of somites and heart, structures of mesodermal origin, and increase in the body length in more than 50% of the treated chick blastoderms. A synthetic fragment of human seminal plasma inhibin, a nonapeptide fragment of C-terminal end, also exhibited similar effects. In some cases the treatments resulted in completely abnormal development while in some increase in the number of somites was associated with abnormality in the anterior region. Our results demonstrate that human seminal plasma inhibin does not act as an inhibitor of mesoderm induction in the chick embryo but in amniotes inhibin-related molecules may have a role as mesoderm enhancers.

Amino Acid Sequence↗

PubMed1993

Occurrence and de novo biosynthesis of follicle stimulating hormone (FSH) in benign and malignant conditions of human breast.

We report the occurrence as well as biosynthesis of a pituitary hormone, follicle stimulating hormone (FSH) in human breast. Using immunoperoxidase localization technique, both FSH and beta-FSH were localized in cytoplasm of epithelial cells but not in stromal cells. Immunostaining was more intense in benign and malignant specimens as compared to normal. In vitro radiolabelled precursor experiments with breast tissue explants indicate de novo synthesis of FSH. Human milk had higher concentrations of FSH as compared to serum. In gonads, FSH is involved in the cellular growth, differentiation and function. The presence of higher levels of FSH in benign mammary tumors and breast cancer when compared to normal breast supports the suggestion that FSH might have a role in the process of breast malignant transformation.

Breast↗

PubMed1993

Human prostatic inhibin suppresses tumor growth and inhibits clonogenic cell survival of a model prostatic adenocarcinoma, the Dunning R3327G rat tumor.

Prostatic inhibin (PI) is a M(r) 10,700 protein found in human seminal plasma and is secreted by the prostate. Recognition of alteration of PI levels in prostatic diseases prompted us to investigate its effect on an animal prostatic adenocarcinoma model, the Dunning R3327G rat tumor. PI not only inhibited in vitro growth of tumor cells but also suppressed tumor growth in vivo. A dose-dependent inhibition of both the clonogenic cell growth and rate of proliferation (DNA synthesis) was observed in tumor cell cultures incubated with purified PI. These inhibitory activities were similar in both androgen-dependent and androgen-independent Dunning tumor cell lines. A functional decapeptide of PI was also found to inhibit Dunning tumor cell colonies in a dose-dependent manner. Daily injection of purified PI into tumor-bearing rats suppressed the tumor growth. A 58% reduction in tumor weight and a 2-fold reduction in tumor growth rate were observed over a 15-day treatment period. Continued treatment with PI significantly suppressed the tumor growth rate by nearly 3-fold. These findings clearly demonstrate a potential application of PI for treating human prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1993

Immunoperoxidase localization and denovo biosynthesis of a 10.5-kDa inhibin in benign and malignant conditions of human breast.

Using immunocytochemistry, we report the occurrence of a 10.5-kDa inhibin in human breast tissue specimens obtained from normal, fibroadenoma and adenocarcinoma cases. The immunostaining for inhibin was confined to the cytoplasm of the epithelium and myoepithelium cells. Expression of inhibin increased in following order: normal (1+); adenocarcinoma and lobular carcinoma in situ (2+) and fibroadenoma (4+). Breast explants has the ability of denovo biosynthesis of inhibin in vitro. In view of the growth modulating regulatory properties of 10.5 kDa inhibin, our findings are suggestive of the potential role of inhibin in breast pathology.

Adenocarcinoma↗

PubMed1993

A comparative study on expression of prostatic inhibin peptide, prostate acid phosphatase and prostate specific antigen in androgen independent human and rat prostate carcinoma cell lines.

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immunohistochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.

Acid Phosphatase↗

PubMed1993

Antifertility effects in female rats immunized with human seminal plasma inhibin.

Adult female rats were actively immunized with sperm-coating protein (10.4 KDa) human seminal plasma inhibin (HSPI). Following 8 weeks of immunization at 2.5 micrograms and 5 micrograms doses of HSPI with Freund's complete adjuvant, antifertility effects were observed in 63% (5/8) and 88% (7/8) of animals, respectively. Estrous cycle was not affected in experimental group. Thus, the present study suggests the potential use of HSPI for immunocontraception in females.

Animals↗

PubMed1993

Effect of synthetic nonapeptide (Thr-Cys-Ser-Val-Ser-Glu-Trp-Gly-Ile) on ovarian follicular development in the bull frog Rana tigrina (Daud).

Effect of synthetic nonapeptide (Thr-Cys-Ser-Val-Ser-Glu-Trp-Gly-Ile) representing the amino acid sequence 86-94 of human seminal plasma was studied on the ovarian follicular growth in the bullfrog R. tigrina during preparatory phase of reproductive cycle. Daily (except on Sundays) injections of 10 micrograms nonapeptide for one month caused a significant increase in ovarian weight and number of second growth phase (SGP) or vitellogenic oocytes. The results suggest that the nonapeptide is biologically active in amphibians also.

Amino Acid Sequence↗

PubMed1993

Studies on the carboxyl terminal peptides of human seminal plasma inhibin (HSPI). Chemical synthesis and in vivo biological activity of the disulfide loop peptide 67-94 of HSPI.

Observation of contradictory results with the in vitro assays for inhibin-like activity of the carboxyl terminal 28 amino acid peptide 67-94 with a disulfide loop, of human seminal plasma inhibin (HSPI), prompted us to synthesize both the linear and the cyclic peptides and test their ability to suppress the circulating levels of follicle stimulating hormone (FSH) in vivo in adult male rats. The linear peptide [Cys(Acm)73,87] 67-94 of HSPI was synthesized by solid-phase peptide synthesis using fluorenylmethyloxycarbonyl (Fmoc) chemistry and a continuous-flow technology. The peptide was cyclized by direct iodine oxidation of the S-diacetamidomethyl peptide in dilute solution. In the in vivo assay the linear peptide did not affect the levels of FSH, whereas the cyclic peptide suppressed the levels of FSH significantly. Thus, the carboxyl terminal region of HSPI does have inhibin-like activity and perhaps has the active core of the protein.

Amino Acid Sequence↗

PubMed1992

An enzyme-linked immunosorbent assay for the detection of human seminal plasma inhibin.

A simple and sensitive enzyme-linked immunosorbent assay (ELISA) is described for the measurement of inhibin in urine and seminal plasma. Standards used cover a range from 50 ng to 0.05 ng/0.1 ml with a detection limit of 0.098 ng/0.1 ml. Coefficients of variation for intra-assay precision and for inter-assay precision were obtained and compared favourably with RIA. Given the ease of application, this technique is an useful alternative to existing radioimmuno-assays for this peptide.

Enzyme-Linked Immunosorbent Assay↗

PubMed1992

Passive immunization against prostatic 'inhibin' peptide as a male contraceptive.

Passive immunization of adult male hamsters for 12 weeks against peptide (As-PIP), a sperm coating antigen, resulted in selective elevation of the blood levels of FSH, impairment of spermatogenesis, and complete infertility when males were mated with normal cycling females. Passive immunization of male marmosets with As-PIP for 8 weeks was also effective and was reversible, without causing any obvious change in mating behaviour. These preliminary studies in hamsters and marmosets indicate that antibodies to a prostatic 'inhibin' peptide represent a promising new approach to male contraception.

Animals↗

PubMed1992

Possible involvement of the accessory sex glands in the regulation of pituitary hormones.

A time-course alteration in the blood levels of gonadotrophin was evaluated in male rats aged 49 days after: (a) removal of the seminal vesicles, (b) bilateral orchidectomy, or (c) bilateral orchidectomy together with removal of the seminal vesicles. Age-matched sham-operated animals served as controls. Removal of the seminal vesicles resulted in elevation in the blood levels of LH, FSH and prolactin compared to controls. As expected, bilateral orchidectomy also resulted in the elevation of serum gonadotrophins. In the absence of both the seminal vesicles and the testes, LH and FSH levels were increased further compared to orchidectomy alone. Thus the present study suggests the presence of a feedback mechanism between the seminal vesicles and pituitary which is more pronounced in the absence of the testes.

Animals↗

PubMed1992

Patterns of inhibin and FSH localization in endometrium of baboon (Papio anubis) during menstrual cycle and early pregnancy.

Immunoreactive 10.5 KDa moiety of inhibin and hFSH was present in the baboon endometrium during menstrual cycle, early pregnancy and in castrated animals treated with steroid hormones, estrogen and/or progesterone. Endometrial differences during the menstrual cycle altered the intensity of immunostaining of inhibin and FSH. Maximum staining was observed in late luteal phase for both the hormones. In early pregnancy (35th day), the conceptus increased the staining for inhibin in the adjoining endometrial glands. Treatment of castrated animals with steroids for 14 days caused increased staining for inhibin. Maximum staining was observed when treated with estradiol or progesterone, whereas combination of estrogen and progesterone treatment decreased the staining reaction. In conclusion, both inhibin and FSH were localized in baboon endometrium and were under the influence of estrogen and progesterone.

Animals↗

PubMed1992

Seminal inhibin--prospects for immunocontraception.

Passive immunization of adult rats, hamsters and marmosets with rabbit anti-seminal inhibin resulted in complete or partial block of fertility. The antiserum treatment presumably neutralized endogenous inhibin resulting in an unopposed rise in circulating FSH. This probably led to a refractoriness of the testes to FSH resulting in complete spermatogenic arrest. Nevertheless, there was no change in the mating behaviour of the animals. The antibodies also affected the epididymal spermatozoa by causing large scale agglutination.

Animals↗

PubMed1992

Antifertility effects in rats actively immunized with 80 kDa human semen glycoprotein.

A 80 kDa human sperm antigen has been identified using the serum of an infertile woman having circulating antisperm antibodies. The antigen was then purified to homogeneity by gel permeation chromatography using HPLC (protein PAK-125 column) system and on FPLC (superose-12 column) system. The antigen was found to be a glycoprotein. The antigen was mainly localized in the postacrosomal region of the human sperm, while it was localized in the head region of the rat sperm as demonstrated by immunofluorescent staining. The presence of this antigen was also demonstrated in the human prostate and endometrium and in the rat testis; epididymis and the prostate by immunocytochemical staining. The purified protein upon active immunization in female rats caused infertility in 100 percent animals. While in male rats it caused infertility in 90 percent animals. On morphometric analysis of testicular tissue it was observed that there was no significant change in spermatogonia and spermatocytes, but significant decrease in spermatids and sperm number as well as daily sperm production in the immunized male rats. The epididymal spermatozoa were markedly reduced in number and were largely found to be agglutinated. The results suggest that 80 kDa human sperm antigen appears to be a suitable candidate for immunocontraception both in male and female.

Animals↗