A. R. Sheth

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.

Effect of prolactin on metabolism of human spermatozoa.

The effect of prolactin on adenyl cyclase, rate of fructose utilization, and glucose oxidation by human spermatozoa was studied. Prolactin stimulated all of these processes at a concentration generally available in seminal plasma. These results suggest that prolactin plays an important role in the energy metabolism of human spermatozoa.

Serum and urinary prostatic inhibin-like peptide in benign prostatic hyperplasia and carcinoma of prostate

The levels of immunoreactive prostatic inhibin-like peptide (PIP), having follicle-stimulating hormone suppressing properties, were estimated in the sera and urine samples of patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC) as compared to age-matched controls. Significantly elevated serum PIP levels in BPH (107.8 +/- 19 ng/ml) and PC (88.7 +/- 9 ng/ml) patients were observed as compared to those in control men (10.2 +/- 1 ng/ml). Unlike serum, in urine high levels of PIP in BPH (294 +/- 49 micrograms/24 h) and extremely low levels in PC (23.6 +/- 5 micrograms/24 h) patients were seen as compared to control values (137.6 +/- 10 micrograms/24 h). Furthermore, striking differences were observed between the urinary PIP levels of BPH and PC patients. The results of the present investigation thus indicate the possible use of urinary PIP as a biological marker for prostate cancer.

Ectopic Production of Human Chorionic Gonadotrophin by Human Breast Tumours

The incidence of tumours ectopically producing the human chorionic gonadotrophins was studied in patients with breast cancer. Specific radioimmunoassay of subunits of HCG was utilized. Nine out of 65 patients with carcinoma of breast showed the presence of circulating HCG. Patients with other pathological conditions of breast tissue did not show any evidence of circulating HCG.

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.

Circulating levels of prolactin in human breast cancer.

Serum prolactin concentrations were measured by radioimmunoassays in 98 patients with established carcinoma of breast, 12 patients with cystic mastitis and 10 patients with gynaecomastia and compared with that of age matched normal control women. The serum prolactin levels in the patients with breast cancer, gynaecomastia or cystic mastitis were observed to be similar to that in normal women. It was interesting to note that the levels of prolactin in the luteal phase of the cycle were higher than that in the early follicular phase in normal women.

Isolation and characterization of ovine testicular and ovarian inhibin.

Low-molecular-weight (< 1500 daltons) peptides with inhibin activity have been isolated from sheep testes and ovaries by simple gel filtration. These peptides were capable of inhibiting the ovarian weight increase in hCG-primed immature female mice and also of suppressing the post-castration rise of serum FSH levels in adult male rats, suggesting similarities in their biological properties. Both testicular and ovarian inhibin were typsin sensitive and heat stable at 100 degrees C for 30 min and were shown to act by interfering with the production of a hypothetical FSH-RH.

Ectopic production of human placental lactogen by human breast tumors

Serum samples from 72 patients with established carcinoma of the breast were investigated for ectopic presence of hPL. Further, the relationship of ectopically‐secreted hPL and hCG‐β in breast cancer was investigated. Ten of 72 patients examined had detectable hPL and 12 had detectable hCG‐β, at 1–2 ng/ml serum sensitivity of the assay. The presence of hPL in serum of breast cancer patients was found to be independent of that of hCG‐β. Sera of 13 patients with cystic mastitis, five with fibroadenoma, two with acute inflamation of breast, 20 normal women (non‐pregnant) and 20 normal men did not show any detectable serum hPL or hCG‐β at the above mentioned sensitivity of the assay. Since these hormones were not detectable in normal men, normal non‐pregnant women, and in patients having other pathological conditions of breast, the possible use of them as markers in cancer is expected.

Immunocytochemical localisation of follicle stimulating hormone (FSH) in normal, benign and malignant human prostates.

Immunocytochemical localisation of follicle stimulating hormone (FSH) was carried out in normal, benign and malignant human prostates by indirect immunoperoxidase technique. Positive staining was observed in the epithelial cells of all the three categories, while the stromal cells showed a weakly positive reaction in a few specimens. The brown reaction product was dispersed in the cytoplasm of the epithelial cells. These observations demonstrate the presence of immunoreactive FSH-like peptide in human prostate. The significance of FSH in the aetiopathology of prostatic disorders is discussed.

Normalization of visual fields following bromocriptine treatment in hyperprolactinemic patients with visual field constriction

Two patients with galactorrhea-amenorrhea and bilateral visual field defects were studied. Routine radiologic examination of each patient revealed a normal sella turcica and no demineralization of the posterior clinoid process. Serum prolactin levels were elevated (patient V. G., 80 ng/ml; patient S. R., 204 ng/ml). Within 2 months of bromocriptine therapy, the serum prolactin levels were normal (patient V. G., 12.21 ng/ml; patient S. R., 8.25 ng/ml) and the bilateral visual field defects were corrected. Bromocriptine has been shown to control prolactin secretion in patients with prolactin-secreting pituitary tumors. Normalization of restricted visual fields following bromocriptine therapy indicates the possibility of an anatomical regression of pituitary hyperplasia or an underlying prolactin-producing microadenoma. It is speculated that the modality of functional galactorrhea reflects hyperplasia of the lactotrophs preceding a nodular and ultimately an adenomatous change. The continuous and prolonged administration of bromocriptine may prevent such a progressive sequence. Further experience is required to validate this possibility.