Androgen dynamics <i>in vitro</i> in the human prostate gland. Effect of oestradiol-17β

Giorgi, Eleonora P.; Stewart, Joan C.; Grant, J. K.; Shirley, I. M.

doi:10.1042/bj1260107

Cited by 32 publications

(6 citation statements)

References 11 publications

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“…The amount of steroid in the tis¬ sue remains proportional to the supply, and the steroid clearance from the tissue is maintained fairly constant. This is in keeping with the findings in human normal prostate (Giorgi et al 1971(Giorgi et al , 1972. In the hyperplastic canine prostate, entry and metabolism vary as in normal glands and there is no great increase in uptake at the higher steroid supply.…”

Section: Discussionsupporting

confidence: 82%

“…The results presented here show that the general pattern of androgen uptake and metabolism in vitro in canine prostate is essentially the same as in the human gland (Giorgi et al 1971(Giorgi et al , 1972. Similar proportions of testosterone, androstenedione and 5a-dihydrotestosterone enter the tissue and are irreversibly metabolized, while the uptake of 5a-dihydrotestosterone is much greater than that of the other two steroids.…”

Section: Discussionmentioning

confidence: 55%

“…5a-Dihydrotestosterone and androstenedione, but not testosterone, are released unchanged from the tissue in measurable amounts. It has also been observed that androstenedione interferes with (Giorgi et al 1972; E. P. Giorgi, . M. Shirley, J. C. Stewart & J. K. Grant, unpublished observations), suggests the existence of a specific carrier system for the transport of androgens into prostatic cells.…”

Section: Discussionmentioning

confidence: 93%

“…Because of the similarities between the two species, as well as the differences, it was thought to be of interest to compare dynamic studies of steroid-tissue interaction of normal and hyperplastic canine prostate with previous investigations of human prostate (Giorgi, Stewart, Grant & Scott, 1971 ; Giorgi, Stewart, Grant & Shirley, 1972). The present paper reports the results of experiments of superfusion of slices of prostate from 15 dogs (11 adult and 4 older than 6 years) with a medium containing testoster¬ one and androstenedione (androst-4-ene-3,17-dione), each labelled with a different isotope, or with medium containing [14C]testosterone and 5a-dihydro[3H]testosterone.…”

Section: Introductionmentioning

confidence: 99%

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Androgen Dynamics in Vitro in the Canine Prostate Gland

Giorgi¹,

Grant²,

Stewart³

et al. 1972

Journal of Endocrinology

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The uptake and metabolism of androgens by canine prostate in vitro were studied by means of an experimental design which consisted of superfusion of prostate slices with a medium containing [4-14C]androstenedione and [6,7-3H]testosterone, or [4-14C]testosterone and 5\g=a\-dihydro[1,2-3H]testosterone. The entry or transfer of steroids into the slices, the irreversible metabolism, the conversion between the steroids and their uptake or tissue retention were measured at the steady state. A similar proportion of the three androgens entered the tissue and was irreversibly metabolized. Conversion of testosterone into 5\g=a\-dihydrotestosterone was much greater than the interconversion of testosterone and androstenedione. The prostate slices retained 5\g=a\-dihydrotestosterone in a concentration up to four times that in the medium, whereas testosterone and androstenedione were retained to a smaller extent.By increasing the steroid concentration in the perfusing medium from 0\m=.\03 to 1\m=.\30 \g=m\mol/l, it was shown that the systems regulating entry, uptake and metabolism of the androgens were not saturated within this range of concentration. No substantial differences were observed in the regulation of tissue\p=m-\androgen interaction in vitro between five normal and four hyperplastic canine prostates. This was in contrast with previously reported findings that, in man, normal and hyperplastic prostatic tissue respond in a different way to an increase in steroid concentration in the medium.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Androgen Dynamics in Vitro in the Canine Prostate Gland

Giorgi¹,

Grant²,

Stewart³

et al. 1972

Journal of Endocrinology

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“…This design permits the separate measurement of the fraction of perfused steroids that is transported into the tissue (i.e. 'entry'), the extent of retention in the tissue, or 'uptake', and the removal of the steroid from the tissue, either by release or metabolism (Giorgi et al, 1971(Giorgi et al, , 1972a. Evidence has been obtained that the mechanism of androgen transport has some specificity.…”

mentioning

confidence: 99%

Androgen dynamics in vitro in the human prostate gland. Effect of cyproterone and cyproterone acetate

Giorgi

Shirley

Grant

et al. 1973

Biochemical Journal

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Hyperplastic and adenocarcinomatous human prostatic tissue was superfused in vitro with radioactively labelled androst-4-ene-3,17-dione, testosterone and 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one), with and without addition of the anti-androgens cyproterone and cyproterone acetate. Cyproterone competitively inhibited the entry of the androgens into the majority of the tissues, whereas cyproterone acetate increased this entry. These findings indicated that transport of androstenedione, testosterone and 5alpha-dihydrotestosterone into prostatic tissue is performed by a specific mechanism, possibly involving a carrier situated in the cell membrane. The extent of metabolism of the three androgens was also modified: formation of 5alpha-dihydrotestosterone from testosterone, and of the latter from androstenedione, was decreased by cyproterone and increased by the acetate. Acetate was more effective than cyproterone in decreasing the ;uptake' of the perfused androgens by the tissue; at the same time, it increased the androgen clearance from the tissue. As cyproterone acetate is the more potent of the two anti-androgens, the possibility that these findings in vitro are related to the different anti-androgenic potency exhibited by the two compounds in vivo is discussed. ;Uptake' of the two anti-androgens and the response to their action on androgen dynamics were similar in adenocarcinomatous and hyperplastic glands.

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Male Sex Hormones, Analogs, and Antagonists

Brueggemeier

2010

Burger's Medicinal Chemistry and Drug Discovery

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The steroid testosterone is the major circulating sex hormone of the male and serves as the prototype for the androgens, the anabolic agents, and androgen antagonists. The endogenous androgens are biosynthesized from cholesterol in various tissues in the body; the majority of the circulating androgens are made in the testes under the stimulation of the gonadotropin luteinizing hormone ( LH ). The reduction of testosterone to dihydrotestosterone is necessary for the androgenic actions of testosterone in many androgen target tissues such as the prostate; the oxidation of testosterone by the enzyme aromatase produces estrogens. The androgenic actions of testosterone and dihydrotestosterone are due to their binding to the androgen receptor, followed by nuclear localization, dimerization of the receptor complex, and binding to a specific DNA sequence. This binding of the homodimer to the androgen response element leads to gene expression, stimulation or repression of the synthesis of new mRNA, and subsequent protein biosynthesis. The synthetic androgens and anabolics were prepared to impart oral activity to the androgen molecule, to separate the androgenic effects of testosterone from its anabolic effects, and to improve upon its biological activities. Novel nonsteroidal androgens, termed selective androgen receptor modulators, were developed to impart agonist activity in selective tissues. Drug preparations are used for the treatment of various androgen‐deficient diseases, for the therapy of diseases characterized by muscle wasting and protein catabolism, for postoperative adjuvant therapy, and for the treatment of certain hormone‐dependent cancers. The two major categories of androgen antagonists are the antiandrogens, which block interactions of androgens with the androgen receptor, and the inhibitors of androgen biosynthesis and metabolism. Such compounds have therapeutic potential in the treatment of acne, virilization in women, hyperplasia and neoplasia of the prostate, and baldness and male contraception.

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Androgen dynamics in vitro in the human prostate gland. Effect of oestradiol-17β

Cited by 32 publications

References 11 publications

Androgen Dynamics in Vitro in the Canine Prostate Gland

Androgen Dynamics in Vitro in the Canine Prostate Gland

Androgen dynamics in vitro in the human prostate gland. Effect of cyproterone and cyproterone acetate

Male Sex Hormones, Analogs, and Antagonists

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