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GADIJA ROSSIER and C. G. PIERREPOINT

Summary.

The metabolism of C21- and C19-steroids by sheep myometrium in vitro has been investigated. At 134 days of gestation, extensive interconversion of progesterone and 20α-dihydroprogesterone was demonstrated, the reaction favouring the reduced form. Low yields only of 20β-dihydroprogesterone and 17α-hydroxyprogesterone were obtained from either precursor. Saturation of the 4-ene bond resulted mainly in the formation of 5α-reduced compounds whilst evidence was obtained for the presence of both 3α- and 3β-hydroxysteroid dehydrogenase activities as opposed to that of a steroid C17-20 lyase.

Similar incubation studies with [4-14C]androstenedione and [1,2-3H]epitestosterone at term indicated a low metabolizing ability of the tissue for these steroids. The main metabolites isolated were 5α-reduction products whilst no 5β-reductase activity could be demonstrated. Interconversion of the two substrates was also shown and testosterone bearing both labels was isolated in low yield. There was little evidence that sheep myometrium at this stage of gestation utilizes these C19-steroids as precursors for oestrogen formation.

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C. G. PIERREPOINT and P. DAVIES

Prostatic hypertrophy is androgen-dependent although the measurement of circulating levels of plasma steroids has not provided the expected information explaining the onset of this condition. Should another route be available to allow for testicular influence on the prostate, then other avenues become available to explain the age-related changes that occur in this organ.

A possible direct anatomical link is provided between the testes and the prostate by the excurrent duct system (i.e. seminiferous tubules, rete testis, vasa efferentia, epididymal ducts and the vasa deferentia). Such a connection might provide the means by which androgenic hormones could be transported from their site of origin to the target organs without having to enter the general circulation. Skinner & Rowson (1967, 1968) showed that severing the vasa deferentia caused a reduction in weight and fructose and citric acid content

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GADIJA ROSSIER and C. G. PIERREPOINT

Summary.

Ovine myometrium obtained at 127 and 119 days of gestation was incubated in vitro with [4-14C]oestrone and [6,7-3H2]oestradiol-17α, and [4-14C]oestrone and [6,7-3H2]oestrone-3-sulphate, respectively. It was considered significant that oestrone was converted mainly to the much more potent oestradiol-17β with very little transformation to the 17α-epimer. A high level of sulphatase activity was demonstrated by the formation of oestrone and oestradiol-17β from oestrone sulphate whereas the isolation of small amounts of oestrogen-3-sulphates also provided evidence of sulphotransferase enzyme activity in this tissue.

These findings are discussed in connection with steroid metabolism by the sheep fetus and placenta and the possible significance of the metabolites isolated with regard to hormonal action in the myometrium.

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BARBARA M. JOHN and C. G. PIERREPOINT

Tenovus Institute for Cancer Research, Welsh National School of Medicine, The Heath, Cardiff CF4 4XX

(Received 27th November 1974)

Studies on the sheep have provided more information concerning the hormonal changes that precede parturition than those on any other mammal. The implications of some of the findings are uncertain but a composite picture is gradually emerging.

The ability of sheep placenta to convert C19-steroids to oestrogens (Ainsworth & Ryan, 1966; Pierrepoint, Anderson, Griffiths & Turnbull, 1970a) and their sulphates (Pierrepoint, Anderson, Harvey, Turnbull & Griffiths, 1971) has been well demonstrated although neither a source nor the species of such potential precursors has been found.

Two of the most active C21-steroid-metabolizing enzymes in the sheep placenta are the 20α-hydroxysteroid dehydrogenase and the 3β-hydroxysteroid dehydrogenase-Δ45-isomerase with the consequent formation of large amounts of progesterone and 20α-dihydroprogesterone (Ainsworth & Ryan, 1967; Pierrepoint et al., 1970b;

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K. Queen, C. B. Dhabuwala and C. G. Pierrepoint

Summary. Accessory sex glands were removed from rats which were then allowed to mate with females.

Ablation of the ventral prostatic lobes appeared to have no affect on the animals' fertility whereas removal of the dorsolateral lobes or of the seminal vesicles induced complete infertility. Excision of the coagulating glands caused infertility in 12/16 males.

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C. G. PIERREPOINT, P. DAVIES and D. W. WILSON

Summary.

Unilateral castration and unilateral vasectomy both bring about a reduction in the androgen-dependent activity of the RNA polymerase enzymes of the ipsilateral lobes of the prostate and seminal vesicles compared to that of the equivalent organs on the contralateral side. After unilateral orchidectomy (i.e. the epididymis was not removed with the testis), the ipsilateral lobes of the prostate were maintained at the same level of activity as those on the intact side. The epididymides, in the absence of the testes but maintained by exogenous testosterone, sustained the prostate and seminal vesicles at a level not achieved in their absence. The epididymis, in the absence of the ipsilateral gonad but maintained by the contralateral testis, provided a greater sustaining influence on the prostate and seminal vesicles than did the testis and epididymis separated from the target organs by vasoligation.

The evidence suggests that the epididymides are able to modulate the function of the prostate and seminal vesicles and that this influence is achieved through an intact ductus deferens. The unilateral effect of castration would seem not to be due solely to the removal of the testis but rather to the simultaneous excision of the androgen-maintained epididymis.

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C. G. PIERREPOINT, P. DAVIES, D. MILLINGTON and BARBARA JOHN

Summary.

Ligation of the deferential vein of the rat has been shown to bring about a reduction in the androgen-dependent activity of the prostatic RNA polymerase enzyme. In the dog, the content of androgens in this vein is of the order of that found in the testicular vein and many times higher than that of peripheral plasma. It seems that the cauda epididymidis alone is sufficient to maintain the ipsilateral lobes of the prostate and seminal vesicles providing an intact ductus deferens and contralateral testis are retained.

The results are discussed in relation to the hypothesis that the deferential vein of the dog and rat may serve as a direct transporting system for androgens from the epididymis to the prostatic complex.

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A. B. M. ANDERSON, C. G. PIERREPOINT, T. JONES, K. GRIFFITHS and A. C. TURNBULL

Summary.

The metabolism, in vitro, of isotopically-labelled pregnenolone and progesterone by foetal and adult sheep adrenals has been investigated. Both substrates were almost completely metabolized by the adult tissue, whereas, in the case of the foetus, only pregnenolone showed extensive metabolism. The adult adrenal converted pregnenolone mainly to cortisol, corticosterone and 11-deoxycortisol, whereas corticosterone was the major product from progesterone. The foetal adrenal, on the other hand, yielded mainly progesterone from pregnenolone with only a small conversion to the corticosteroids. The substrate, progesterone, was transformed, in the main, to 11-deoxycorticosterone. No 3β-hydroxysteroid sulphokinase-transferase activity was demonstrated in either tissue. The importance of these findings and the probable pathways involved in the formation of the biosynthetic products are discussed.

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C. G. PIERREPOINT, P. DAVIES, M. H. LEWIS and D. B. MOFFAT

Tenovus Institute for Cancer Research, The Heath, Cardiff CF4 4XX, and Department of Anatomy, University College, Cardiff

Species predisposition to various diseases can at times be related to ecological factors such as the immediate environment, the life-style and diet or to inherent biochemical make-up or anatomical configuration. It is, however, as yet unexplained why man and dog appear to be alone in the animal kingdom in their susceptibility to prostatic hypertrophy. The gland appears to be unequivocal in its essential function and is universally androgen-dependent. It is of interest therefore to determine any common factor that discriminates against animals of these two species and leaves all others apparently immune.

The prostate of man and dog, unlike that of the bull, boar, stallion and ram, is compact and the ductus deferentes pass through it to reach the urethra (Text-fig. 1). Prostatic hypertrophy becomes clinically important, however, because the gland completely encircles

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Muazaz Younes, Bronwen A. J. Evans, N. Chaisiri, Y. Valotaire and C. G. Pierrepoint

Summary. High-affinity and low-capacity molecules that bind 5α-dihydrotestosterone and oestradiol-17β have been demonstrated in the canine epididymis. The molecules were shown to be proteinaceous in nature, thermolabile and sedimented in a sucrose density gradient with a coefficient of 8S with respect to bovine serum albumin.

Only minor differences were found for dissociation constants for oestradiol-17β (3·5 ± 2·74 × 10−10 m) and 5α-dihydrotestosterone (4·2 ± 10·75 × 10−10 m) (means ± s.d.) in the three anatomically distinct regions of the epididymis.