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R. G. GOSDEN
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SUMMARY

The uptake in vivo of tritiated oestradiol-17β has been compared in young and aged ovariectomized CBA/H-T6 mice by examining the levels of radioactivity in tissues 1 h after injection. The specificity of oestradiol uptake was demonstrated by previous treatment of some animals with either diethylstilboestrol or progesterone. The levels of radioactivity in whole tissue extracts were similar in both age groups for the uterus, hypothalamus, cerebrum and serum, but the uptake in the pituitary gland was significantly lower in old mice. There was no evidence of altered hormone metabolism with age.

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R. G. GOSDEN
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Department of Physiology, University Medical School, Teviot Place, Edinburgh, EH8 9AG

(Received 20 March 1978)

Ageing female rats maintained under standard laboratory lighting conditions (14 h light: 10 h darkness) frequently enter a state of persistent vaginal cornification because the pituitary gland fails to provide an ovulatory surge of gonadotrophic hormones. The ovaries of such animals become dominated by growing and cystic follicles as the corpora lutea disappear. The concentrations of prolactin in the pituitary gland and the circulation during persistent oestrus are known to be raised for at least part of the day (Clemens & Meites, 1971; Mallampati & Johnson, 1974; Shaar, Euker, Riegle & Meites, 1975; J. E. Beach, R. G. Gosden & J. W. Everett, unpublished observations). A possible antigonadotrophic role of prolactin in the aetiology of the persistent oestrous condition should be considered because of the known inverse relationship between the release of prolactin and gonadotrophins

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R. G. GOSDEN
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C. READHEAD
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Recently a single hypothalamic hormone, termed luteinizing hormone releasing hormone (LH-RH), capable of releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary has been chemically characterized and synthesized (Matsuo, Arimura, Nair & Schally, 1971; Matsuo, Baba, Nair, Arimura & Schally, 1971) and has been shown to be biologically active in several species (Schally, Arimura & Kastin, 1973). Initial attempts to demonstrate LH-RH action in 4-day cyclic mice treated with sodium barbitone in pro-oestrus were unsuccessful because barbitone did not consistently block ovulation (R. G. Gosden, unpublished results). In this report we demonstrate the action of LH-RH in adult female mice as shown by the induction of ovulation and the increase of serum LH.

Young virgin (8–14 weeks) CFLP mice (Carworth Europe) were injected with 3 i.u. pregnant mare serum gonadotrophin (Intervet) i.p. at 16.00–17.00 h without reference to the stage of the oestrous cycle. Approximately 44 h later

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M. J. Faddy
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R. G. Gosden
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R. G. Edwards
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The rates of follicle growth and death have been estimated by a mathematical method in A, CBA, RIII and A × CBA strains of mice for which differential follicle counts were available. These rates were not uniform throughout life but were specific for the immature and mature phases of life. Significant heterogeneity of the rate estimates for particular follicle stages was also identified between strains and between intact and hypophysectomized mice, which explained the differing life-time patterns of follicular utilization in these animals.

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C D Smyth
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R G Gosden
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A S McNeilly
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S G Hillier
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Abstract

Inhibin is a putative gonadal paracrine factor produced by FSH-stimulated granulosa cells. To assess the paracrine function of inhibin further, preantral follicles (approx. 240 μm) with attached thecal cells were isolated mechanically from immature rat ovaries and cultured individually in vitro for 5 days in medium containing homologous serum and FSH. After 5 days, follicles had grown to preovulatory size (approx. 470 μm) with a commensurate increase in oestradiol secretion but not progesterone. Immunoneutralization of endogenous inhibin resulted in a significant decrease in oestradiol secretion and an increase in progesterone accumulation. When antiserum-treated follicles were supplemented with exogenous inhibin, oestradiol secretion was restored and progesterone accumulation was reduced. Aromatase substrate (androstenedione) levels were too low to measure, regardless of antiserum treatment. However, follicles treated with inhibin antiserum in the presence of exogenous androstenedione also exhibited oestradiol levels similar to untreated controls while progesterone accumulation remained elevated. We interpret these data as evidence that inhibin secreted by FSH-stimulated granulosa cells exerts a physiologically significant paracrine function in the follicle wall. Based on previous observations that inhibin stimulates androgen synthesis by isolated thecal/interstitial cells, it is proposed that granulosa-derived inhibin promotes thecal androgen synthesis and hence oestrogen synthesis during preovulatory follicle development. The antiserum-induced increase in progesterone accumulation is most probably explained by reduced metabolism of C21 steroid substrate to androgen in thecal/interstitial cells deprived of inhibin. It is concluded that inhibin is a physiological modulator of follicular steroidogenesis which exerts its effect at the level of thecal cell androgen synthesis.

Journal of Endocrinology (1994) 140, 437–443

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R. G. GOSDEN
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J. A. RUSSELL
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J. CLARKE
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I. PIPER
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A. S. McNEILLY
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Treatment of rats with bromocriptine between days 5 and 8 after the post-partum mating resulted in suppression of serum prolactin levels and caused luteal regression. Although this treatment led to embryonic resorption when suckling was prevented by removing litters soon after birth, the diapausing embryos of animals nursing a litter of eight pups were unaffected by the treatment. These results suggest that the high levels of prolactin and progesterone in the circulation during lactation are not responsible for maintenance of the diapausing state.

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J. A. Russell
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R. G. Gosden
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E. M. Humphreys
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R. Cutting
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N. Fitzsimons
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V. Johnston
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S. Liddle
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S. Scott
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J. A. Stirland
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ABSTRACT

Oxytocin secretion is inhibited by opioids, and oxytocin is important in parturition. The effects on parturition of morphine, a relatively selective μ-opioid receptor agonist, were studied in the rat. Morphine or vehicle with or without the opiate antagonist naloxone were administered immediately after the birth of the second pup and the subsequent course of parturition was recorded in a total of 80 rats. Both s.c. morphine (10 mg/kg) and intracerebroventricular (i.c.v.) morphine (18 μg through a previously implanted cannula) interrupted parturition, delaying the birth of the sixth pup after treatment to 187·3 ± 35·9 (s.e.m.) min and 195·4 ± 19·5 min respectively, compared with 46·4 ± 3·7 and 66·1 ± 17·5 min after vehicle alone. The dose of morphine given i.c.v. had no effect when given s.c. Naloxone given concurrently prevented the effects of morphine. Eventually the rate of parturition in the morphine-treated groups recovered. Perinatal pup mortality rate was not increased when morphine was given to the mothers, but it did inhibit the expression of normal intrapartum maternal behaviour.

Pup mortality was increased 48 h post partum by morphine given during parturition, and it reduced the proportion of rats with normal maternal behaviour 24 h post partum. Morphine did not affect spontaneous or oxytocin-stimulated contractile activity of the parturient uterus in vitro. The concentration of oxytocin in trunk blood plasma was decreased 40 min after i.c.v. morphine (24·3 ± 3·9 vs 39·3± 6·5 pmol/l in controls), as was vasopressin (7·2 ± 1·5 vs 19·7 ± 4·5 pmol/l in controls). Intravenous infusion of oxytocin (2–5 mU/min for 144·3 ± 8·2 min; total infused 448·5 ± 61·9 mU) after i.c.v. morphine re-started parturition; all pups were born to these rats (mean time to pup 6, 110·3 ± 12·7 min) before the i.v. vehicle-infused rats given i.c.v. morphine re-started (mean time to pup 6, 406·3±125·2 min).

It is concluded that morphine given during parturition acts centrally through opioid receptors to inhibit oxytocin secretion, and impairs the expression of maternal behaviour. Reversal of the effects of morphine on parturition by i.v. oxytocin demonstrates the important role of oxytocin in fetus ejection and expulsion.

Journal of Endocrinology (1989) 121, 521–536

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