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R. C. JONES
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Since the effects of injecting oxytocin into ewes just after artificial insemination were to be tested, the experiment described was designed to determine a range of doses of synthetic oxytocin which would produce 'milk let-down' in ewes. Intramuscular injection was chosen as the most practical route of administration since it was planned to use a large number of sheep in the subsequent experiments.

Martinet & Denamur (1960) have shown that both massage of the udder and i.v. injection of 10–50 m-u. oxytocin cause similar increases in intramammary pressure in goats and sheep and Debackere & Peeters (1960) and Debackere, Peeters & Tuyttens (1961) have shown that intramammary pressure in ewes was increased by distension of the vagina; a similar response was obtained by i.v. injection of 20–50 m-u. oxytocin. Since Fitzpatrick (1960) had found that oxytocin injected i.v. was 2·25 and 2·5 times more potent than when injected i.m., the

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R. C. JONES
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The oral administration of 5 mg. quinestrol (3-cyclopentyl ether of ethinyl oestradiol) has been shown to inhibit ovulation in normal women (Skerlavay & Epstein, 1967); presumably the quinestrol blocks the release of gonadotrophins. In parabiotic rats, Giannina, Steinetz & Meli (1967) used daily administration of oral quinestrol to block hypersecretion in the castrated male.

In the present study, hemicastrated adult female rats were used to test the prolonged pituitary blocking effect of a single oral dose of quinestrol. At the time of the unilateral ovariectomy, the rats recieved 1 mg. quinestrol by gavage. Animals were killed at approximately 2-day intervals after operation. At autopsy the remaining ovary (the left) was removed and weighed. Hemicastration produces a compensatory hypertrophy of the remaining ovary which may be prevented by oestrogen administration (Peterson, Edgren & Jones, 1964). If quinestrol is long-acting when given orally and suppresses pituitary gonadotrophic function it should decrease this

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R. L. Kennedy
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T. H. Jones
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INTRODUCTION

Cytokines are soluble polypeptides released from cells of the immune system. Their production in endocrine glands and their actions on hormone-responsive cells is currently a subject of intense research interest. There is strong evidence for the involvement of cytokines in the pathogenesis of autoimmune diabetes and thyroid disease. In addition they may regulate the growth and differentiated function of cells as they are known to do in the reticuloendothelial system. Cytokines may thus contribute to the development of functional endocrine disturbances and neoplasms. They are also involved in bone modelling processes and their action may be disturbed in disorders of bone. Greater understanding of the effects of cytokines will give insight into normal regulatory processes in endocrine tissues and may lead to therapeutic advances. The aim of this article is to review these actions and to speculate as to their physiological and pathophysiological significance as well as

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R. B. JONES
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N. W. NOWELL
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Preputial gland activity is related to social experience (Hucklebridge, Nowell & Wouters, 1972) and these glands are thought to affect the fighting behaviour of mice through the release of an aggression-promoting pheromone (Mugford & Nowell, 1970). The coagulating glands are thought to be the source of an aggression-inhibiting pheromone (Haug, 1971). The present study provides direct evidence for the function of these glands by assessing the aggression-inducing properties of combinations of the gland secretions with bladder urine or water.

A number of 4-month-old male T.O. albino mice were killed. The preputial and coagulating glands were dissected out and the gland contents were gently squeezed into bladder urine or into the same amount of distilled water. Six test substances were used: (1) bladder urine, (2) bladder urine+preputial gland secretion, (3) bladder urine + coagulating gland secretion, (4) water, (5) water + preputial secretion, and (6) water + coagulating gland secretion.

The 15 mice used

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GWYNETH E. JONES
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A. R. BOYNS
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SUMMARY

Intravenous injections of synthetic LH-RH stimulated LH secretion in male dogs. Pretreatment with 50 μg oestradiol-17β, 60 or 165 min but not 15 min before LH-RH, inhibited LH secretion. Injection of 0·1–10 μg oestradiol 165 min before administration of LH-RH, blocked LH secretion. Basal plasma LH levels before LH-RH administration were lower in dogs given oestradiol than in controls.

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W. D. BOOTH
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R. JONES
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SUMMARY

The metabolism of radioactively labelled testosterone, 5α-dihydrotestosterone, 5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol by the rabbit epididymis and prostate has been investigated in vitro and in vivo. In vitro, the rate of conversion of testosterone to 5α-reduced androgens was low in both glands. Varying the nature of the tissue preparation, age of animal or incubation medium did not improve the situation substantially. However, the rabbit prostate and epididymis metabolized 5α-reduced androgens readily. The prostate was particularly efficient at interconverting 5α-androstane-3α,17β-diol and 5α-dihydrotestosterone, whereas the capacity of the epididymis to carry out this step was much lower. Small amounts of 5α-androstane-3,17-dione and androsterone were also identified. Both glands interconverted 5α-dihydrotestosterone and 5α-androstane-3β,17β-diol to a comparable degree.

Following the intravenous injection of 3H-labelled testosterone, significant levels of 3H-labelled 5α-dihydrotestosterone were found in the prostate and epididymis within 30 min. Furthermore, 5α-androstane-3α,17β-diol was detected in both glands. In blood plasma, the ratio of radioactively labelled testosterone: 5α-dihydrotestosterone was 2: 1, i.e. similar to that for endogenous steroids. The intravenous injection of 3H-labelled 5α-androstane-3α-17β-diol gave rise to much higher amounts of 5α-dihydrotestosterone in the prostate than in the epididymis, whereas the reverse was found for the levels of unmetabolized diol.

The results indicate that the prostate and epididymis of the adult rabbit differ in their capacity to metabolize 5α-reduced androgens and that both glands depend to a large extent on the relatively high levels of 5α-dihydrotestosterone and 5α-androstanediols present in the peripheral circulation, rather than the metabolism of testosterone in situ.

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D. I. R. JONES
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Metronidazole (1-β-hydroxyethyl-2-methyl-5-nitroimidazole; Flagyl, May & Baker Ltd.), an effective trichomonicidal agent, has recently been credited with widespread metabolic and endocrine effects including biochemical and clinical improvement of thyrotoxicosis (Taylor, 1962, 1965). Harden, Chisholm & Cant (1967), however, found no antithyroid action in either healthy volunteers or thyrotoxic patients but noted improvement of exophthalmos in 9 of 13 patients. The present trial was undertaken to establish the effect of metronidazole on exophthalmos.

Twenty thyrotoxic patients were selected; all had established exophthalmos with a minimum exophthalmometer reading of 20 mm. The patients had all been treated for thyrotoxicosis between 1·5 and 17 yr. previously (mean 5·9 yr.), either with radioactive iodine (14), surgically (3) or with antithyroid drugs (3). At the time of inclusion in the trial 6 patients were euthyroid and 11 were hyperthyroid and receiving antithyroid drugs; three had become hypothyroid after radioactive iodine therapy and were receiving thyroxine.

A

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R. B. JONES
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N. W. NOWELL
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SUMMARY

The aversive properties of urine of castrated male mice receiving varying doses of testosterone phenylpropionate was assayed using males housed in groups of six as subjects. The aversive efficacy of the urine was found to rise with an increase in androgen levels. There was a delay of 5 days before the exogenous androgen exerted any effect on the aversive properties of the urine. This delay indicated that the aversive factor might be a pheromonal substance released from an androgen-dependent tissue, rather than being an excreted androgen metabolite.

The results are discussed in terms of androgen levels and possible territorial functions.

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GWYNETH E. JONES
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A. R. BOYNS
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SUMMARY

Intravenous injections of synthetic luteinizing hormone releasing hormone (LH-RH) stimulated LH secretion in male dogs. An i.m. injection of 0·025–2·5 mg oestradiol-17β given 2·5 h but not 24 h before administration of LH-RH blocked LH secretion. Diethylstilboestrol (2·5 mg) also blocked LH secretion but meso-dihydrodibutylstilboestrol (2·5 mg) was without effect. Testosterone (2·5 and 25 mg), dihydrotestosterone (2·5 mg), 5α-androstane-3α, 17β-diol (2·5 mg), 5α-androstane-3β, 17β-diol (2·5 mg), 5α-androstane-3α, 17α-diol (0·125 mg), 5α-androstane-3β, 17α-diol (0·125 mg) and progesterone (25 and 50 mg) did not prevent LH-RH stimulation of LH secretion.

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R. B. JONES
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N. W. NOWELL
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Male mouse urine contains an androgen-dependent aversive pheromone which discourages prolonged investigation, by male conspecifics, of an area marked with such urine (Jones & Nowell, 1973a). The source of this pheromone lies in the coagulating glands, whose secretion, when combined with bladder urine, causes avoidance (Jones & Nowell 1973b). The present study describes an attempt to inhibit the release of the aversive pheromone of male mice by treatment with the potent anti-androgen cyproterone acetate. Thus the open-field responses of male mice to the urine of either oil-injected or cyproterone acetate-injected males were compared. Some confirmation of the inhibitory action of cyproterone acetate upon sex accessory organ responses to endogenous androgens was gained by recording the weights of the ventral prostate, preputial and coagulating glands.

Twenty 24-day-old male t.o. albino mice were divided into two groups of ten; the first group received s.c. injections of cyproterone acetate (2 mg/mouse)

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