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Biomedical subjects

F S French

Publications and source records attributed to F S French.

At least 109 records · Page 6Linked to original sources
PubMed1979

Characterization of different forms of the androgen receptor.

Three forms of the androgen receptor have been characterized at high ionic strength in partially purified cytosol and nuclear fractions of rat ventral prostate, epididymis, testis, and seminal vesicle by ion exchange chromatography on phosphocellulose, gel filtration in Sephadex G-200, and sedimentation in sucrose gradients. The three forms have the following properties, respectively: elution from phosphocellulose at 0.15--0.20, 0.3--0.5, and 0.20--0.32 M KCl; gel filtration radii of 53, 36, and 22 A; sedimentation coefficients of 5.0S, 3.6S, and 3.0S; frictional ratios of 1.65, 1.4, and 1.0; and molecular weights of 115,000, 55,000, and 29,000. In testis and epididymis cytosol, the 53 A, 5S form was more abundant than the 36 A, 3.6S form. In ventral prostate, the 36 A, 3.6S receptor was the predominant form. Variable amounts of all three forms were observed in seminal vesicles. Conversion from 36 A, 3.6S to 22 A, 3.0S was induced by heating ventral prostate cytosol and could be blocked by serine protease inhibitors. The 22 A, 3.0S receptor fragment from heated prostate cytosol was similar in size and symmetry to receptor extracted in 0.5 M KCl from prostate nuclei labeled in vivo. Extracts of epididymis and seminal vesicle nuclei contained both 36 and 22 A forms.

Animals↗
PubMed1979

Is FSH required for maintenance of spermatogenesis in adult rats?

Administration of FSH antiserum to adult rats for 14 or 30 days had no or little effect on body, testis or accessory sex gland weights, androgen-binding protein, testosterone levels, germ cell numbers or fertility, thus indicating a relative insensitivity of the testis to withdrawal of FSH. Unlike immature rats, therefore, which do require FSH to initiate spermatogenesis, adult rats do not need this hormone to maintain spermatogenesis.

Age Factors↗
PubMed1977

In vitro synthesis of rat testicular androgen-binding protein (ABP).

Testicular tissue from immature and adult rats shows in vitro synthesis of androgen-binding protein (ABP). The ABP synthesis is dependent on a complete tissue culture medium, the incubation temperature and the age of the rats. ABP synthesis is inhibited at 0 degrees C or in the presence of cycloheximide, puromycin or sodium fluoride. Immature (17-25-day-old rat) testes showed a higher rate of ABP synthesis per 100 mg tissue than adult rat testes during 'baseline' conditions (no additions to the medium). Addition of NIH-FSH-S10 or testosterone to the medium increases the production of ABP by the testicular minces. The in vitro techniques have proved to be useful for studies of direct hormonal influence on the Sertoli cell protein synthesis.

Aging↗
PubMed1977

9S binding protein for androgens and progesterone.

A steroid binding protein fraction with a sedimentation coefficient of approximately 9 S (molecular weight approximately equal to 200,000) has been identified in 105,000 X g supernatants of several androgen-responsive organs. Highest concentrations were found in epididymis and testis, but small amounts were detected in prostate, seminal vesicle, kidney, submandibular gland, and lung. The 9S protein binds [3H]dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and [3H]progesterone (4-pregnene-3,20-dione) with equilibrium binding constants of approximately 10(5) M-1 and 10(6) M-1, respectively. The concentration of 9S binding sites in epididymis is approximately 10(-11) mol/mg of supernatant protein, which is at least 10(5) times greater than the concentration of androgen receptor. 9S binding protein appears to be a nonsecretory, intracellular protein and has properties different from the andorgen receptor. It is unretarded on DEAE-Sephadex chromatography at pH 8.0, and its sedimentation rate on sucrose gradients is not altered at high ionic strength (0.4 M KCl). Like the androgen receptor, its binding activity, which is maximal between pH 7 and 9.5, is heat labile, decreased by sulfhydryl reagents, and enhanced by 2-mercaptoethanol. It is suggested that because of its high concentration and low affinity, 9S binding protein may function in the intracellular accumulation of compartmentalization of androgens or progesterone.

Androstane-3,17-diol↗
PubMed1976

Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate.

Androgen receptors in crude and partially purified 105,000 X g supernatant fractions from rat testis, epididymis, and prostate were studied in vitro using a charcoal adsorption assay and sucrose gradient centrifugation. Androgen metabolism was eliminated during receptor purification allowing determination of the kinetics of [3H]-androgen-receptor complex formation. In all three tissues, receptors were found to have essentially identical capabilities to bind androgen, with the affinity for [3H] dihydrotestosterone being somewhat higher than for [3H] testosterone. Equilibrium dissociation constants for [3H] dihydrotestosterone and [3H] testosterone (KD = 2 to 5 X 10(-10) M) were estimated from independently determined rates of association (ka congruent to 6 X 10(7) M-1 h-1 for [3H] dihydrotestosterone and 2 X 10(8) M-1 h-1 for [3H] testosterone) and dissociation (t 1/2 congruent to 40 hr for [3H] dihydrotestosterone and 15 h [3H] testosterone). Evaluation of the effect of temperature on androgen receptor binding of [3H]testosterone allowed estimation of several thermodynamic parameters, including activation energies of association and dissociation (delta H congruent to 14 kcal/mol), the apparent free energy (delta G congruent to -12 kcal/mol), enthalpy (delta H congruent to -2.5 kcal/mol), and entropy (delta S congruent to 35 cal col-1 K-1). Optimum receptor binding occurred at a pH of 8. Receptor stability was greatly enhanced when bound with androgen. Receptor specificity for testosterone and dihydrotestosterone was demonstrated by competitive binding assays. The potent synthetic androgen, 7 alpha, 17 alpha-dimethyl-19-nortestosterone, inhibited binding of [3H] testosterone or [3H] dihydrotesterone nearly as well as testosterone and dihydrotestosterone while larger amounts of 5 alpha-androstane-3alpha, 17 beta-diol and nonandrogenic steroids were required. Sedimentation coefficients of androgen receptors in all unfractionated supernatants were 4 and 5 to 8 S. Differences in sedimentation coefficients were observed following (NH4)2SO4 precipitation which did not influence the binding properties of the receptors. These results, together with measurements of3alpha/beta-hydroxysteroid oxidoreductase activity in vitro, suggest that organ differences in receptor binding of [3H] dihydrotestosterone and [3H] testosterone in vivo result from relative differences in intracellular concentrations of these androgens rather than from differences in receptor affinities.

Androgens↗
PubMed1976

Further characterization of the androgen receptor in rat testis.

Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules.

Animals↗
PubMed1976

Hormones and hormonal target cells in the testis.

Studies over the last few years have greatly increased our knowledge about target cells for sex hormones and gonadotropins in the testis. A diagram illustrating our present state of knowledge is given in Fig. 1. LH is the principle stimulus of testosterone secretion by the Leydig cells. Direct effects of estrogens and androgens on these cells might modulate the response to LH. Androgens are apparently influencing the differentiation and the contractility of peritubular cells. FSH is the principle stimulus for Sertoli cell secretory function before puberty, although androgens are acting synergistically with FSH. After puberty, androgens alone are capable of maintaining on optimal secretory function of the Sertoli cells. In addition to normal secretory activity of the Sertoli cells, direct stimulation of the germ cells by androgens is needed in order maintain spermatogenesis.

Age Factors↗
PubMed1976

Secretion and role of androgen-binding proteins in the testis and epididymis.

The Sertoli cell appears to be a target cell for both FSH and androgen. FSH stimulates the Sertoli cell to produce an androgen-binding protein (ABP) which may serve to increase the accumulation of androgen in the seminiferous tubular epithelium and make it available for binding by intracellular androgen receptors. This might be one way by which FSH enhances the action of androgen on spermatogenesis. Androgen acts on the Sertoli cell to increase its response to FSH resulting in increased production of ABP and of other substances which exert trophic effects on spermatogenesis.

Androgens↗
PubMed1975

Testicular androgen binding protein (ABP) - a parameter of Sertoli cell secretory function.

Using ABP as an index of Sertoli cell secretory function, several important features of the Sertoli cell have emerged: 1. The stimulation of ABP production by FSH clearly points to the Sertoli cell as a target cell for FSH (3,4,9-16,21,24). 2. The dramatic effects of androgens on ABP production both in immature and mature rats also suggest that the Sertoli cell is a target cell for androgen (3,12,14,16,25). 3. The striking reduction in ABP production in the cryptorchid testis raises the question whether impairment of Sertoli cell function is the primary reason for the loss of germ cells that occurs in this condition (20). 4. Drugs like nitrofurazone or ethionine, or X-irradiation only slightly affect the secretory function of the Sertoli cells (ABP production), indicating that these treatments most probably have direct effects on the germ cells as well. Thus, measurement of ABP production rate is a very important tool in order to evaluate how hormones, drugs and physical injuries might affect the secretory function of the Sertoli cell. This test system might be of great use in order to study the physiology and hormonal regulation of the Sertoli cells. It might also be valuable in pharmacological and toxicological studies.

Age Factors↗