Binding of testosterone, 5α-dihydrotestosterone and 5α-androstane(3α- and 3β),17β-diols to serum proteins in the rat

Tenniswood, Martin; Abrahams, Pamela P.; Winterton, V.; Bird, C. E.; Clark, A. F.

doi:10.1016/0022-4731(82)90096-6

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…Nevertheless, a number of investigations have found this protein to be lacking or undetectable in the plasma of common laboratory rodents such as rats, mice, and golden hamsters (Lea & Stoa, 1972;Corvol & Bardin, 1973;Stupnicki & Bartke, 1976;Renoir et al, 1980;Tenniswood et al, 1982). In the present study, however, a specific SBP has been identified in the Djungarian hamster.…”

Section: Discussioncontrasting

confidence: 71%

Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters

Gustafson¹,

Damassa²,

Pratt³

et al. 1989

Reproduction

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The binding of sex steroids to plasma proteins was examined in post-natal Djungarian and golden hamsters. With dihydrotestosterone or testosterone as ligands, steady-state polyacrylamide gel electrophoresis revealed 2 androgen binding components in the plasma of young Djungarian hamsters of both sexes. The fast-moving component exhibited a low affinity and high capacity for androgens and corresponded to albumin in stained gels. In contrast, the slow moving component was a \g=b\-globulin with high affinity (Ka = 109 m \ m=-\ 1) and low capacity for androgens, and was identified as a specific sex steroid-binding protein (SBP; also SHBG). This SBP did not bind oestrogens or corticosteroids and was electrophoretically distinct from corticosteroid-binding globulin (CBG). In addition, this protein did not appear to be of testicular origin because it was present in immature females and in immature males that had been castrated for 8 days. Plasma concentrations of SBP in males as measured by a diethylaminoethyl-cellulose binding assay were low at birth, became significantly elevated shortly thereafter when plasma androgen values were also elevated, and subsequently fell to low levels during puberty. These changes follow the same general pattern that has been described for other mammals, including humans, during this period of reproductive development. Although the significance of elevated SBP concentrations during prepuberty has yet to be determined, it appears that the increased concentrations of high-affinity androgen binding in the plasma of Djungarian hamsters plays a role in the asynchronous pubertal development of the testes and accessory organs which occurs in this species. The post-natal SBP pattern in females was similar to that observed in males. Plasma SBP levels were low or undetectable in adults of both sexes. As previously described for adult golden hamsters, the plasma of post-natal male and female golden hamsters lacked a specific SBP: androgen binding in this species is apparently limited to albumin and CBG.

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Section: Discussioncontrasting

confidence: 71%

Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters

Gustafson¹,

Damassa²,

Pratt³

et al. 1989

Reproduction

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“…Changes in the extent of binding of the androgens to plasma proteins did not occur and hence would not influence the avail¬ ability of hormone to the prostate. These results are consistent with the lack of a specific, high-affinity rat plasma protein for binding androgens, leaving princi¬ pally albumin to account for the observed binding (Tenniswood et al 19826). …”

Section: Discussionsupporting

confidence: 88%

Androgen metabolism and regulation of rat ventral prostate growth and acid phosphatase during sexual maturation

Orlowski

Bird²,

Clark³

1988

Journal of Endocrinology

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Androgen metabolism and the regulation of rat ventral prostate cell proliferation and secretory function were examined during sexual maturation. Changes in acid phosphatase (AP) characteristics were measured as a marker of androgen-dependent prostatic secretory function. In immature (21-day-old) rats, total AP activity per cell was low (14.2 +/- 1.3 mol p-nitrophenol phosphate hydrolysed/h per mg DNA); it increased threefold as the weight, protein and DNA contents of the prostate increased to adult (65-day) levels. This corresponded with significant (P less than 0.001) increases in the staining intensities of three of the four bands of secretory AP on isoelectric focusing gels. The extent of inhibition of AP by tartrate decreased at the same time. Secretory AP is known to be relatively tartrate-resistant. The changes in AP activity occurred after prostatic 5 alpha-dihydrotestosterone (5 alpha-DHT) levels increased from 4.6 +/- 0.7 pmol/mg DNA (21 days) to reach a peak of 17.6 +/- 2.3 pmol/mg DNA at 58 days. Prostatic 5 alpha-DHT concentrations were always higher than testosterone levels. Prostatic 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Adiol) levels were lower than 5 alpha-DHT levels except on day 58 when levels peaked dramatically at 26.2 +/- 5.5 pmol/mg DNA. Changes in prostatic 5 alpha-DHT and 3 alpha-Adiol levels corresponded with changes in 5 alpha-reductase and 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) activities. The oxidative reaction of 3 alpha-HSOR was approximately fourfold higher than the reductive reaction, indicating a preference for the formation of 5 alpha-DHT. The plasma levels of testosterone, 5 alpha-DHT and 3 alpha-Adiol cannot account for their respective prostatic levels, indicating the importance of the steroid-metabolizing enzymes in regulating intracellular androgen levels. Changes in the AP characteristics could be correlated with the androgen status of the prostate.

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“…The kinetics of T and DHT in the liver are described by using a flow-limited compartmental model. Metabolism of T to DHT via 5␣-reductase in the liver is modeled with a Michaelis-Menten term, and linear terms are included for the general metabolic clearance of T and DHT in the liver (49). The rate equations for T and DHT in the liver are given by…”

Section: Model Structure: Pharmacokinetic Componentmentioning

confidence: 99%

“…LH upregulates the production of T and, hence, DHT, which in turn downregulates LH, creating a negative feedback loop (12). In the blood, T and DHT bind to serum albumin, which appears to play a role in regulating transport and tissue uptake dynamics (15,33,49).…”

mentioning

confidence: 99%

Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats

Potter¹,

Zager²,

Barton³

2006

American Journal of Physiology-Endocrinology and Metabolism

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The testicular-hypothalamicpituitary axis regulates male reproductive system functions. Understanding these regulatory mechanisms is important for assessing the reproductive effects of environmental and pharmaceutical androgenic and antiandrogenic compounds. A mathematical model for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the adult rodent ventral prostate was developed on the basis of a model by Barton and Anderson (1997). The model describes the systemic and local kinetics of testosterone (T), 5␣-dihydrotestosterone (DHT), and luteinizing hormone (LH), with metabolism of T to DHT by 5␣-reductase in liver and prostate. Also included are feedback loops for the positive regulation of T synthesis by LH and negative regulation of LH by T and DHT. The model simulates maintenance of the prostate as a function of hormone concentrations and androgen receptor (AR)-mediated signal transduction. The regulatory processes involved in prostate size and function include cell proliferation, apoptosis, fluid production, and 5␣-reductase activity. Each process is controlled through the occupancy of a representative gene by androgen-AR dimers. The model simulates prostate dynamics for intact, castrated, and intravenous T-injected rats. After calibration, the model accurately captures the castration-induced regression of the prostate compared with experimental data that show that the prostate regresses to ϳ17 and 5% of its intact weight at 14 and 30 days postcastration, respectively. The model also accurately predicts serum T and AR levels following castration compared with data. This model provides a framework for quantifying the kinetics and effects of environmental and pharmaceutical endocrine active compounds on the prostate. rodent ventral prostate; androgen receptor; testosterone; 5␣-dihydrotestosterone; testicular-hypothalamic-pituitary axis THE HYPOTHALAMUS, PITUITARY, AND TESTES produce endocrine hormones responsible for regulation of the prostate and other male sexual functions (12, 46). Exogenous endocrine active compounds can disrupt these processes. Some pesticides (e.g., vinclozolin and linuron) are known to have antiandrogenic activity (19,20). Toxic effects of antiandrogens in male rodents range from developmental effects such as reproductive malformations, retained nipples, and undescended testes to pubertal effects such as delayed puberty and reduced weights of prostate and other reproductive organs. In the pharmaceutical setting, therapeutic drugs such as finasteride, dutasteride, bicalutamide, and flutamide are used to treat benign prostatic hyperplasia and/or prostate cancer by inhibiting androgendependent growth processes.The mechanisms of action of antiandrogens are generally of two forms. The first is the androgen antagonist, which binds to the androgen receptor (AR) but does not stimulate DNA transcription, such as the pharmaceutical compounds flutamide and bicalutamide or the environmental compound vinclozolin. The second is the 5␣-reductase inhibitor, which blocks th...

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Binding of testosterone, 5α-dihydrotestosterone and 5α-androstane(3α- and 3β),17β-diols to serum proteins in the rat

Cited by 16 publications

References 18 publications

Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters

Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters

Androgen metabolism and regulation of rat ventral prostate growth and acid phosphatase during sexual maturation

Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats

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