Some effects of testosterone on the rat ventral prostate

1. Labelled testosterone, injected directly into the ventral prostate of castrated rats became associated, in part, with a cytoplasmic high-molecular-weight fraction, fraction ;A'. 2. The label present in fraction ;A' was found to be mainly associated with dihydrotestosterone. 3. Unlike fraction ;A' from testosterone-pelleted castrated rats, fraction ;A' obtained from untreated castrated rats, 48h or more after castration, was strongly inhibitory towards Escherichia coli RNA polymerase in vitro. 4. The inhibition of RNA polymerase by fraction ;A' from castrated rats was not changed by the addition of testosterone or dihydrotestosterone in vitro, but pre-heating it to 80 degrees C resulted in a loss of its inhibitory capacity. 5. Fraction ;A' from castrated rats contained ribonuclease activity. The elution profile of ribonuclease activity from Sephadex columns indicated that this activity was responsible for the inhibitory effect on the RNA polymerase assays. 6. It is concluded that, unlike the inhibitor present in the uterus of ovariectomized rats (Talwar, Segal, Evans & Davidson, 1964), no direct connexion exists between the steroid-binding capacity of prostatic fraction ;A' and its effect on E. coli RNA polymerase activity in vitro.     

Some problems with testosterone determination

Testosterone is the main male sex hormone which determination is useful for assessment of androgen status. It seems that serum levels of testosterone, when assayed by commonly used methods, do not correlate with clinical parameters. One of the causes may be that these assays are suitable for determination of total testosterone, but not for measurement of biologically active forms of this hormone. The aim of this review is to present usefulness of testosterone measurement and its bioactive forms determination as well as factors influencing on their levels.     

Nonsteroidal substances that affect serum free testosterone

Several steroid hormones affect free testosterone (FT) levels in blood by competing with testosterone for binding sites on testosterone-binding globulin (TeBG). However, the effect of endogenous nonsteroidal substances in serum has not been reported. Some of these potential modifiers of FT were studied using equilibrium dialysis. Nonesterified fatty acids at 0.9 mM elevated FT approx 10% at pH 7.4. Investigation of the curvilinear relationship of percent FT (pFT) vs pH showed that pH-dependent changes of testosterone binding to albumin were responsible for a small linear increase in pFT with decreasing pH. The greater portion of the curvilinear increase of pFT with decreasing pH was due to fatty acids competing with testosterone for TeBG binding sites. Ketone bodies significantly affected FT (7.5% elevation) only at levels found in diabetic ketoacidosis. Sodium ions improved binding 11% when 7 mM was compared to 157 mM sodium, but physiological changes in sodium would result in only +/- 1% changes in FT. Very low levels (0.03 mM) of calcium may be essential for normal testosterone binding to TeBG since 1.0 mM EGTA raised FT by 75%. This study shows that dialysis at 37 degrees C should not be performed overnight, that thimerosol should not be used as a preservative, and that the dialysis buffer should contain physiological concentrations of sodium and calcium.     

Effect of free fatty acids on the bioavailability of plasma testosterone and dihydrotestosterone

Free fatty acids (FFA) are known to interfere with the binding of thyroid hormone and estrogens to circulating proteins, but their effect on androgen binding is unknown. The effect of linoleic, oleic and palmitic acids at physiological concentrations on the binding of testosterone (T) and dihydrotestosterone (DHT) to circulating proteins was evaluated in vitro, using equilibrium dialysis and ammonium sulfate precipitation techniques. The results indicate that FFA can inhibit T binding to albumin and SHBG. They also can inhibit DHT binding to albumin, whereas DHT binding to SHBG is not altered, suggesting that FFA at physiological concentrations may be important regulators of bioavailability of T to tissues.     

Metabolites of testosterone: significance in the vital economy

Testosterone is metabolized by practically every tissue in the body to a large variety of related steroids. The metabolites vary with each tissue and appear to be formed to meet the specific needs of the particular tissue and animal. The many biologic actions of testosterone do not change in parallel in the various metabolites. Many of the metabolites show interesting differences in their relative biologic effects. A large number and variety of steroid-metabolizing enzymes (oxidoreductases, reductases, hydroxylases, aromatases) are involved. Some have been partially purified. The 17 beta-oxidoreductases of the cytosol of the guinea pig liver and kidney have been purified and characterized.     

The biological and clinical significance of nicks in human chorionic gonadotropin and its free beta-subunit.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits, alpha and beta. Nicks or missing peptide linkages have been found in the beta 44-52 region of the beta-subunit of hCG, whether from pregnancy or trophoblast disease. This article reviews recent reports about the location of nicks in hCG, their origin and occurrence, their effects on the steroidogenic and receptor-binding activities of hCG, and on the immunological activities of hCG and its free beta-subunit. Taken together, the reports show: (1) nicks occur primarily between beta 47 and beta 48, and to a lesser extent between beta 44 and beta 45; (2) the extent of nicking in hCG samples varies widely, from undetectable to 100 percent of molecules; (3) nicks greatly reduce the steroidogenic activity of hCG in vitro (nicked molecules have less than 20 percent of the activity of the intact hormone); (4) nicks may occur at the trophoblast-myometrial interface or in the circulation by the action of human leucocyte elastase or similar leucocytic protease; (5) hCG testing kits using dimer-specific antibodies may not detect nicked molecules and may give different results from those using other antibodies; (6) hCG international reference preparations and the CR series of hCG standards are variably nicked (10 percent to 20 percent), complicating the problem of discordant hCG results in nick-sensitive assays; (7) results from commonly used immunoassays for measurement of the hCG free beta-subunit vary by as much as tenfold because some of the antibodies employed do not detect nick free beta-subunit.     

Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men

Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.     

歌德与生物学

歌德（Goethe）是德国古典文学和民族文学的杰出代表,也是世界文学史上最杰出的作家之一。青年时代,他的书信体小说《少年维特之烦恼》使他获得了巨大的成功;而他晚年的作品《浮士德》则是他一生丰富的思想总结和艺术探索的结晶,因而与荷马史诗、但丁的《神曲》和莎士比亚的《哈姆雷特》并列为欧洲文学的四大古典名著。歌德在世界文学史上的重要地位是毋庸置疑的,但是他在生物学上的重要贡献就鲜为人知了。     

Unraveling the biological significance of nitric oxide

Independent investigations into the biochemical changes and cytostatic properties induced in immunostimulated macrophages and studies involving the identity and mechanism of action of endothelium-derived relaxing factor led to the finding of a new metabolic pathway which converts L-arginine to nitric oxide and citrulline. The pathway has since been reported in a number of additional cell types including cells in the central nervous system (CNS). In the endothelium and CNS nitric oxide is acting as a signaling agent with the evidence supporting activation of the enzyme guanylate cyclase in the target cell. Nitric oxide is toxic and evidence supports a cytostatic/cytotoxic function as the primary action of macrophage-derived nitric oxide.