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A. A. SHAIKH and D. P. GILMORE

Summary.

Pseudopregnancy (PSP) in the rat was significantly lengthened by a single injection of 20 μg LH or 100 μg FSH on Day 5. Doses of oestradiol ranging from 0·05 to 0·20 μg, injected at this time, also significantly prolonged PSP, whereas larger amounts did not. Neither the antioestrogen ICI 46474, nor progesterone, given early in PSP shortened its duration, the antioestrogen itself significantly extended PSP. Daily injections of 20 μg LH to pseudopregnant animals, starting on Day 5, maintained luteal function even longer than did the single dose. Hysterectomy of LH-treated animals did not further extend PSP indicating that the uterus was not involved in terminating luteal function in these animals. Oestrone, oestradiol and progesterone were measured on Day 8 of PSP, in the ovarian venous blood collected from animals treated with ICI 46474 or progesterone on Day 3, and from others subjected to hemiovariectomy and either X-irradiation or sham irradiation on that day. These measurements failed to reveal suppression of oestrogen secretion and consequent reduction in the secretion of other steroids due to the treatments. It is suggested that oestrogens may play an important rôle in the maintenance of luteal function during PSP by complementing the luteotrophic action of the gonadotrophins.

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W. D. Ratnasooriya, D. P. Gilmore and R. M. Wadsworth

Summary. Insertion of Silastic rods containing the directly acting sympathomimetic drug, methoxamine, adjacent to the epididymis of rats caused a temporary reduction in fertility with no loss of ability to mate. This effect lasted up to 3 weeks. At the time of the maximal antifertility action (3–7 days after insertion), the number of spermatozoa in the ejaculate fell to almost zero, and there was a reduction in the total number of spermatozoa in the epididymis resulting from a significant drop in the number present in the cauda. Methoxamine also caused immotility and decapitation of the remaining epididymal spermatozoa. The indirectly acting sympathomimetics, tyramine and norephedrine, did not affect fertility. It is postulated that methoxamine acts to induce infertility principally by bringing about a reduction of sperm numbers in the ejaculate. This could have been produced either by a failure of the vas and cauda to contract normally at copulation or because the sperm store in the cauda had fallen below a critical threshold level.

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W. D. Ratnasooriya, R. M. Wadsworth and D. P. Gilmore

Summary. The sympathomimetic drugs noradrenaline, methoxamine, tyramine and norephedrine caused rhythmic contractions in isolated human vasa deferentia. Provided the drug was not washed out, these contractions lasted for the entire duration of the experiment (4–6 h). These contractions were mediated via α-adrenoreceptors. Intravenous administration of methoxamine or oxymetazolene to rats or guinea-pigs produced contractions of the vas deferens in vivo in some experiments but was accompanied by severe cardiovascular side effects. A local method of application was developed, using mixtures of tyramine with Silastic prepared as collars specially designed to fit round the vas deferens. Acute and chronic insertion of these slow-releasing devices around the vas deferens of rats produced rhythmic contractions of the vas deferens without any serious side effects.

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W. D. Ratnasooriya, D. P. Gilmore and R. M. Wadsworth

Summary. Local application of collars containing 25% methoxamine, 50% or 75% tyramine or 50% norephedrine to both vasa deferentia of rats caused a reduction in fertility but not in their ability to mate. A gradual return to fertility was seen in those animals which received the lower dose of tyramine or norephedrine, while the other treatments caused a permanent reduction in fertility. The cause of sterility was production of azoospermic ejaculates resulting from either a block in sperm transport in the vas deferens or from a deficiency in the ejaculatory mechanism. Only methoxamine caused a mechanical obstruction of the vas deferens, but it is possible that the other drugs caused a sustained spasm. An emission defect could have been due to transmitter depletion, receptor-specific desensitization or presynaptic α-adrenoreceptor-mediated inhibition. Spermatozoa from the cauda epididymidis were immotile following the treatments.

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H. M. Johnston, A. P. Payne and D. P. Gilmore

Adult female hamsters were treated with a long-acting form of morphine before mating and throughout pregnancy; the drug was gradually withdrawn during lactation. The offspring produced were gonadectomized as adults and tested for their ability to display feminine and masculine sexual behaviour after appropriate hormonal priming. Chronic exposure to morphine during development resulted in males that showed an increase in both feminine and masculine sexual behaviour when compared with controls.

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D. P. GILMORE, R. H. HOOKER and M. C. CHANG

Since the successful establishment of a fistula of the vas deferens in the ram by White, Larson & Wales (1959), various techniques have been devised for the collection of epididymal spermatozoa from bulls, rams and boars. Wierzbowski & Wierzchos (1969) list authors who have undertaken such work. Recently, we have developed a fistula method for the regular collection of epididymal spermatozoa from the rat.

Because of its extremely small diameter, the rat's vas deferens is unsuitable for cannulation and when brought directly to the surface of the skin, it soon becomes obstructed and covered by closure of the skin above it. It can, however, be anastomosed either to the small or to the large intestine by simple implantation and will generally remain open and continue to function indefinitely. Utilizing this principle to construct a fistula of the vas deferens, the following procedure has now been frequently undertaken in mature Sprague-Dawley rats (Charles River CD strain).

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D. P. Gilmore, H. G. Dobbie, A. S. McNeilly and C. H. Mortimer

Summary. Immunoreactive LH-RH was present in all the hypothalamic and cortical extracts of mid-term human fetuses studied and in the cortical tissue removed from the two youngest fetuses. Gonadotrophin-releasing activity of hypothalamic and cortical extracts was demonstrated by the significant rises of circulating LH after infusion into oestrogen and progesterone-primed ovariectomized rats.

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D. J. Kennaway, J. C. Peek, T. A. Gilmore and P. Royles

Summary. Prepubertal ewe lambs were treated with empty or filled melatonin implants. The implants were placed s.c. at birth and pituitary responsiveness to various doses of LHRH, LH/FSH pulsatility and prolactin and melatonin secretion were examined at 10, 19, 28, 36 and 45 weeks of age. Control animals (N = 10) showed no consistent alteration in pituitary responsiveness to LHRH during development. Ewes treated with melatonin (N = 10) had puberty onset delayed by 4 weeks (P < 0·03) but no effect of melatonin on LH or FSH response to LHRH injection was observed at any stage of development. In the control and melatonin-treated ewe lambs the responses to LHRH injection were lower during darkness than during the day at all stages of development. No consistent differences in LH or FSH pulsatility were observed between treatment groups or during development. Prolactin concentrations, however, failed to decrease at the time of puberty (autumn) in the melatonin-treated group. Melatonin-treated ewe lambs maintained normal rhythmic melatonin production which was superimposed on a higher basal concentration and showed the same increase in melatonin output with age as the control ewes. These results indicate that the delayed puberty caused by melatonin implants is not due to decreased pituitary responsiveness to LHRH or to dramatic changes in basal LH or FSH secretion.