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Biomedical subjects

R M Sharpe

Publications and source records attributed to R M Sharpe.

At least 163 records · Page 9Linked to original sources
PubMed1980

Binding of human chorionic gonadotrophin to testicular biopsy tissue from infertile men and the effect of prior treatment with human chorionic gonadotrophin.

The binding of 125I-labelled human chorionic gonadotrophin (HCG) to testicular tissue obtained by biopsy from 27 infertile men has been investigated. Fresh tissue cut into pieces was used for these studies as homogenization and/or freezing severely reduced the ability of testicular tissue to bind HCG. In five infertile men who had a normal endocrine profile and normal testicular histology, 10.3 +/- 1.4 (S.D.) pg 125I-labelled HCG were bound/mg testis, which was similar to binding (7.9 +/- 3.6 pg/mg) to testicular tissue obtained from three apparently normal men who underwent orchidectomy for prostatic carcinoma. However, in five infertile men with germ cell aplasia binding was increased to 16.6 +/- 5.7 pg/mg tissue. Fourteen infertile men were injected 24 h before biopsy with HCG, and this treatment consistently, and in most cases significantly, reduced the testicular binding of 125I-labelled HCG compared with that found in untreated, infertile men. It was concluded that measurement of HCG-binding in testicular biopsy specimens is feasible and may prove useful in assessing similarities between Leydig cell function in man and animals.

Adult↗
PubMed1979

The effect of induced hyperprolactinaemia on Leydig cell function and LH-induced loss of LH-receptors in the rat testis.

Anterior pituitary glands were transplanted beneath the kidney capsule of intact, adult male rats to induce hyperprolactinaemia. This resulted in reduced serum levels of LH and FSH and increased adrenal weight. In pituitary-transplanted rats, testicular hCG-receptor binding was increased by 55 to 175%, whilst the capacity of the testis to secrete testosterone in vitro was greatly reduced. Injection of ovine LH into control and pituitary-transplanted rats resulted in similar percentage reductions in hCG-receptor binding in the two groups. This treatment impaired the in vitro steroidogenic responsiveness of testes from control rats at 24 h after injection, but had no major effect on the already-impaired, steroidogenic responsiveness of testes from pituitary-transplanted rats. Although induction of hyperprolactinaemia resulted in marked changes in Leydig cell function, these alterations were possibly due to the chronically reduced serum gonadotrophin levels in hyperprolactinaemic rats as well as a direct effect of prolactin on the Leydig cell.

Animals↗
PubMed1979

Alterations in steroidogenesis and human chorionic gonadotropin binding in the cryptorchid rat testis.

One month after the induction of cryptorchidism in adult rats, serum levels of LH and FSH were significantly elevated in comparison with sham-operated controls, whereas serum levels of testosterone remained low to normal. Testis weight in cryptorchid rats was reduced by over 66%, and once the extratubular fluid was removed by decapsulation, the reduction in weight was 78%. The basal production of testosterone, pregnenolone, and estradiol in vitro by testes from cryptorchid rats was similar to controls, whereas significantly less androstenedione was produced. Testicular stimulation in vitro with a high dose of hCG (360 pM) resulted in significantly greater production of testosterone, pregnenolone, and estradiol by cryptorchid than by control rat tissue. The in vitro binding of [125I]hCG per testis was decreased in the cryptorchid state to 40% of control values, probably as a result of down-regulation of LH receptors due to the 4-fold elevation of serum LH levels in the cryptorchid rats.

Androgens↗
PubMed1979

Failure of estrogen-induced discharge of luteinizing hormone in lactating women.

Pituitary-ovarian relationships were studied in seven lactating women by measuring the basal plasma concentrations of pituitary and ovarian hormones and their responses to an estrogen provocation test at 7, 30, and 100 days after delivery. The results were compared to a similar group of seven women who did not breast feed. The first ovulation occurred in five of the nonlactating women beteen 43-87 days after delivery, as judged by the urinary excretion of total estrogen and pregnanediol. In all lactating women, ovarian cyclicity was suppressed for at least 150 days after delivery or until weaning. The basal concentration of PRL in lactating women was significantly higher than in the nonlactating women at all three times measured. At 30 and 100 days, the concentration of estradiol was significantly lower in the lactating women, although the basal concentrations of FSH were similar in the two groups. After an injection of 1 mg estradiol benzoate, the concentrations of FSH and LH in plasma were suppressed to a greater extent in lactating than in nonlactating women. In addition, fewer of the lactating group (one of seven and none of seven at 30 and 100 days, respectively) than the nonlactating group (two of seven and five of seven) subsequently showed a rise in the concentration of LH 58--96 h after the estrogen injection (positive feedback). These results suggest that during lactation the hypothalamic-pituitary system is more sensitive to the negative feedback and relatively insensitive to the positive feedback of estrogen.

Adult↗
PubMed1979

Gonadotrophin-induced accumulation of 'interstitial fluid' in the rat testis.

'Interstitial fluid' containing high levels of testosterone (60-250 ng/ml) was recovered from the testes of rats, the amounts increasing with increase in age and testis weight. Injection of 170 i.u. hCG/kg resulted 20 h later in significant increases in interstitial fluid and its testosterone content (300-800 ng/ml). In immature rats this effect of hCG was dose-dependent and time-related and the accumulated fluid contained high levels of potassium and phosphate; levels of sodium, calcium and protein were similar to those in serum. At 20 h after injection of hCG, other testicular changes were (1) increased 'adhesiveness', (2) reduced in-vitro binding of 125I-labelled hCG, and (3) an hCG-induced increase in the testis:blood ratio of hCG in vivo.

Animals↗
PubMed1979

Effect of treatment with an agonist of luteinizing hormone releasing hormone on early maturational changes in pituitary and testicular function in the rat.

Male rats aged 30 days were injected once daily for between 1 and 7 days with 50 ng (D-serine t-butyl6, des-glycine-NH210) luteinizing hormone releasing hormone ethylamide (LH-RH agonist), and pituitary and testicular function were assessed. Treatment for 7 days significantly (P less than 0.02) inhibited maturational increases in the pituitary content and serum concentration of gonadotrophins, testicular luteinizing hormone (LH)-receptor concentration and the testicular capacity to secrete testosterone; the pituitary content and serum concentration of prolactin, the hypothalamic content of LH-RH and testicular weight were unaffected. In rats treated with LH-RH agonist, the initial (2 to 3 days) reduction in testicular LH-receptors and the capacity to secrete testosterone probably resulted from acutely raised levels of LH in the blood, whilst later effects may have resulted from the apparently chronic reduction in serum gonadotrophin levels. The latter may reflect a decrease in pituitary responsiveness to repeated stimulation with LH-RH agonist. Despite the extensive loss of testicular LH-receptors and diminished responsiveness, the concentration of HCG which significantly (P less than 0.05) increased testosterone secretion by the testis in vitro was the same (2 pmol/l) as that for testes from control rats.

Animals↗
PubMed1977

Absence of hCG-like activity in the blood of women fitted with intra-uterine contraceptive devices.

Blood was obtained at various stages of the menstrual cycle from 201 women fitted with intra-uterine contraceptive devices (IUDs), and plasma levels of hCG were determined by radioimmunoassay. Urine samples were obtained from 117 of these women and tested, before and after sephadex gel filtration, in a haemagglutination inhibition test for pregnancy (Pregnosticon). Plasma hCG was undetectable (less than 25 MLU/ml) in all but one of the 201 women and, in this instance, the hCG-assay appeared to be measuring a midcycle peak of LH, as evidenced by high plasma FSH levels. All unextracted urines gave negative results in the Pregnosticon test but, after extraction, 18 of the 117 urines gave positive reactions, most of these being from women at midcycle or in the luteal phase. We conclude that the IUD does not permit the development of the embryo to a point where it is capable of secreting measurable amounts of hCG. Recent claims to the contrary are probably due to cross-reaction of LH or non-specific interference in the assays used for measuring hCG.

Adolescent↗
PubMed1977

The onset and establishment of spermatogenesis in rats in relation to gonadotrophin and testosterone levels.

The concentrations of LH and FSH in the plasma and pituitary gland, and testosterone in the plasma and testes were measured in individual rats between 21 and 180 days of age. Spermatogenesis was quantitated in the same animals and correlations between the various parameters were calculated. The numbers of Sertoli and spermatogenic cells up to pathytene spermatocytes increased in parallel with the peripheral levels of FSH up to days 33 or 35. The concentration of FSH in the plasma started to decrease after day 55, but this decrease could not be correlated with the appearance of any cell type in the testes of the same animals; it was probably due to the high levels of peripheral testosterone at this age. Testicular and plasma levels of testosterone were closely correlated in all age groups studied. The first significant increase occurred between days 39 and 41 and coincided with an increased growth rate of the seminal vesicles and ventral prostate gland. The increase in the concentration of testosterone occurred 10 days after the concentration of LH in the plasma rose to a measurable level. Spermatogenesis had proceeded up to step 16 spermatids at this age.

Aging↗
PubMed1977

Gonadotrophins, testosterone and spermatogenesis in neonatally irradiated male rats: evidence for a role of the Sertoli cell in follicle-stimulating hormone feedback.

Peripheral concentrations of FSH in the male rat seem to be regulated in part by a protein hormone, inhibin, which originates from the testes. In an attempt to ascertain which type of testicular cell secretes inhibin, groups of male rats were irradiated prenatally or on days 4, 6 or 8 of postnatal life, and killed at 21, 51 or 81 days of age together with castrated and intact controls. The concentrations of FSH and LH in the pituitary gland, and FSH, LH and testosterone in the plasma were estimated for each animal, and the numbers of each class of intratubular cell in the testes were calculated. Rats irradiated neonatally had fewer Sertoli cells than controls at all ages studied, while the numbers of Sertoli cells in rats irradiated prenatally were higher than those in controls on day 21. The number of spermatogenic cells was usually decreased in rats irradiated postnatally. In the rats irradiated prenatally normal numbers of spermatogenic cells were found at day 51. Numbers of spermatogenic cells were significantly correlated with the number of Sertoli cells at the ages of 51 and 81 days. The concentrations of FSH in the plasma usually increased in the postnatally irradiated animals on days 21 and 51, but not on day 81; prenatal irradiation did not result in altered levels of FSH at any age. Peripheral levels of LH and testosterone were not affected by irradiation. The concentration of FSH in the plasma was negatively correlated with the number of Sertoli cells in all age groups, whereas significant correlations between the level of FSH and the number of spermatogenic cells were only found at days 51 and 81. It is concluded from these data that the Sertoli cell is the most likely source of inhibin.

Aging↗
PubMed1976

Radioligand receptor assay of FSH.

The assay of FSH by a radioligand receptor assay (RLA) using homogenates of rat testicular tissue incubated for 17 h at 21 degrees C has been assessed. Chloramine-T or lactoperoxidase were used for iodination. The assay gave linear dose-response lines between 30 and 2000 ng sheep FSH/tube, and there was usually no major interference by LH. Two batches of labelled FSH, however, gave assays in which LH showed a striking interaction with FSH. When these batches were avoided and FSH and LH were mixed in ratios that differed less than fourfold, the assay was combined successfully, in the same tubes, with an RLA for LH, using LH and FSH labelled with 131I and 125I respectively. The RLA for FSH was not suitable for assay of FSH in rat serum because of apparent non-specific interference. Assay by RLA of rat FSH, in pituitary homogenates or released during incubation in vitro, gave results which were not closely correlated with those of either conventional bioassay or radioimmunoassay.

Animals↗