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Biomedical subjects

H M Fraser

Publications and source records attributed to H M Fraser.

At least 181 records · Page 10Linked to original sources

Effect of adrenalectomy or castration on the inhibition of gonadotrophin secretion induced by hyperprolactinaemia in the adult male rat.

To investigate the role of adrenal and gonadal steroids in the long-term suppression of gonadotrophin secretion induced by prolactin the effects of adrenalectomy or castration on the serum and pituitary levels of LH, FSH and prolactin and the hypothalamic content of LH releasing hormone (LH-RH) have been studied in adult male rats with hyperprolactinaemia produced by the transplantation of pituitary glands under the kidney capsule. Levels of LH and FSH in serum were significantly suppressed in al intact pituitary-grafted rats. Adrenalectomy on the day of pituitary implantation or 20 days later did not affect the suppression. However, castration on days 0, 28 or 49 after pituitary grafting resulted in a rise in levels of FSH in serum indistinguishable from that in control rats. While the rise in levels of LH after castration on day 0 was the same as the controls, this increase was significantly reduced 2 days after castration on days 28 and 49 after pituitary grafting. Castration resulted in an increase in the pituitary content of LH and a reduction in the hypothalamic content of LH-RH but no change in the pituitary content of FSH. Hyperprolactinaemia did not appear to affect these response. The present results showed clearly that the gonad but not the adrenal must be present for prolactin to exert an inhibitory effect on gonadotrophin secretion.

Adrenalectomy↗

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↗

Changes in the ovaries of rats after immunization against luteinizing hormone releasing hormone.

Rats were immunized against luteinizing hormone releasing hormone (LH-RH) and ovulation and follicular development were studied 12, 24 and 48 weeks later. The abolition of regular cyclic patterns of vaginal smears and the absence of luteal tissue in all but one of 32 rats showed that the immunization was effective in blocking ovulation. Follicular growth varied between rats and appeared to be dependent on whether the inhibition of LH-RH had been sufficient to affect the secretion of basal levels of gonadotrophins. Low levels of gonadotrophins were associated with poor follicular development, uterine atrophy and leucocytic vaginal smears, whereas levels of gonadotrophins similar to those in the dioestrous controls led to adequate follicular growth in the absence of ovulation, the production of cystic follicles, uterine stimulation and persistent vaginal oestrus. A group of rats was ovariectomized 12 weeks after immunization against LH-RH; animals with low antibody titres and large follicles responded with increases in the levels of LH and FSH in the blood, whereas in those with high antibody titres and little follicular development the concentrations of gonadotrophins remained low. The reproductive capacity of rats immunized against LH-RH was tested by caging them with normal male rats from 3 weeks after immunization. Although mating occurred in three rats during the first month, no offspring were produced. No matings occurred in the remaining 41 weeks.

Animals↗

Active immunization of ewes against luteinizing hormone releasing hormone, and its effects on ovulation and gonadotrophin, prolactin and ovarian steroid secretion.

Three Scottish Blackface ewes were immunized against luteinizing hormone releasing hormone (LH-RH) conjugated to bovine serum albumin (BSA) and three control ewes were immunized against BSA alone. When the antibody titre to LH-RH became raised the treated animals failed to show oestrus or ovulate; they had significantly lower levels of plasma luteinizing hormone (LH) and higher levels of prolactin than the controls, whereas the levels of follicle-stimulating hormone (FSH) were unaltered. The integrity of the hypothalamus-pituitary-gonadal system of these animals was then challenged by the injection of a highly active analogue of LH-RH and by ovariectomy. An i.v. injection of 5 microgram D-serine-t-butyl 6 des-glycine-NH2 10 LH-RH ethylamide raised plasma LH and FSH. Ovariectomy caused an eight- and ninefold rise in plasma levels of LH and FSH respectively in controls, but failed to increase plasma levels of LH and FSH in the LH-RH-immunized ewes. Plasma prolactin concentrations in the LH-RH-immunized ewes were significantly reduced by ovariectomy.

Animals↗

Determination of nomifensine by a sensitive radioimmunoassay.

1. A radioimmunoassay (RIA) has been developed for determination of both nomifensine and total nomifensine (nomifensine + conjugated nomifensine) in serum, plasma, and urine. 2. Antibodies were prepared in rabbits by immunization with N-(8-Nomifensine) succinamic acid-bovine serum albumin. 3H-labelled drug was used as tracer. Separation of free from antibody-bound nomifensine was carried out using dextran-coated charcoal. For determination of total nomifensine, the acid-labile conjugate was split by acidification. 3. The limit of detection for nomifensine is 300 pg/ml plasma and the cross-reactivity of the metabolites is less that 1%. The influence of conjugated nomifensine on the results of nomifensine can be corrected. 4. Pharmacokinetics of nomifensine were determined in healthy volunteers after oral administration of 100 mg 14C-labelled drug. Peak levels of 14C radioactivity (2,150 ng/ml), total nomifensine (1,252 ng/ml) and nomifensine (53 ng/ml) appeared within 1.5-2 h; the half-life of elimination from plasma was 1.5-2 hours. The advantages of this routine method are high sensitivity, the requirement of small amounts of plasma, and simple handling.

Administration, Oral↗

Gonadotrophin release by a highly active analogue of luteinizing hormone releasing hormone in rats immunized against luteinizing hormone releasing hormone.

Immunization against luteinizing hormone releasing hormone (LH-RH) in adult male rats produced a progressive decline in LH and FSH in the circulation to low or non-detectable levels. D-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide is an analogue of LH-RH having highly active LH-RH properties in the normal rat. Because it is also immunologically different from LH-RH it can stimulate gonadotrophin release from the anterior pituitary gland of rats immunized against LH-RH without interference from the antibody. The analogue stimulated LH and FSH release in rats 15 weeks after immunization against LH-RH when antibody titre was highest, and after long-term (35 weeks) immunization against LH-RH. D-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide and related analogues are therefore potentially useful for reversing the effects of immunization against LH-RH.

Animals↗

Immunofluorescent localization of sites binding anti-synthetic LHRH serum in the median eminence of the greenfinch (Chloris chloris L.).

With an indirect immunofluorescence technique and an antiserum raised against synthetic LHRH, immunofluorescent granules were observed in fine radially oriented fibres in the palisade layer of the zoma externa in both the anterior and the posterior divisions of the median eminence in the greenfinch. There was no specific immunofluorescence in the tractus supraoptico-hypophyseus. It is concluded that the greenfinch median eminence contains material which is similar to mammalian LHRH.

Animals↗