I only had a chance to read the first study, the others i skimmed, but the first study showed a decrease in SHBG after the administration of DHT.
J Clin Endocrinol Metab. 2002 Apr;87(4):1467-72. Related Articles, Links
Comment in:
J Clin Endocrinol Metab. 2002 Apr;87(4):1462-6.
The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study.
Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS.
Division of Urology, Department of Surgery, University of Oulu, FIN-90014 Oulu, Finland.
The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal penile tumescence once per week or less, andropause symptoms, and a serum T level of 15 nmol/liter or less and/or a serum SHBG level greater than 30 nmol/liter. The mean age was 58 yr (range, 50-70 yr). Of these subjects, 114 men completed the study. DHT was administered transdermally for 6 months, and the dose varied from 125-250 mg/d. General well-being symptoms and sexual function were evaluated using a questionnaire, and prostate symptoms were evaluated using the International Prostate Symptoms Score, transrectal ultrasonography, and assay of serum prostate-specific antigen. Early morning erections improved transiently in the DHT group at 3 months of treatment (P < 0.003), and the ability to maintain erection improved in the DHT group compared with the placebo group (P < 0.04). No significant changes were observed in general well-being between the placebo and the DHT group. Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment. Treatment with DHT did not affect liver function or the lipid profile. Hemoglobin concentrations increased from 146.0 +/- 8.2 to 154.8 +/- 11.4 g/liter, and hematocrit from 43.5 +/- 2.5% to 45.8 +/- 3.4% (P < 0.001). Prostate weight and prostate-specific antigen levels did not change during the treatment. No major adverse events were observed. Transdermal administration of DHT improves sexual function and may be a useful alternative for androgen replacement. As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia, DHT may be beneficial, compared with aromatizing androgens, in the treatment of aging men.
Publication Types:
Clinical Trial
Randomized Controlled Trial
Biochemistry. 2003 Nov 25;42(46):13735-45. Related Articles, Links
Binding analysis of 1alpha- and 17alpha-dihydrotestosterone derivatives to homodimeric sex hormone-binding globulin.
Metzger J, Schnitzbauer A, Meyer M, Soder M, Cuilleron CY, Hauptmann H, Huber E, Luppa PB.
Institute for Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar der Technischen Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany.
Binding studies of the interaction of immobilized 1alpha- and 17alpha-aminoalkyl derivatives of 5alpha-dihydrotestosterone (DHT) with purified N-deglycosylated homodimeric human sex hormone-binding globulin (SHBG) were performed using a surface plasmon resonance biosensor. These 1alpha- and 17alpha-derivatives with spacers of appropriate lengths between the amine function and the steroid ring skeleton enabled privileged, sterically undisturbed, interactions of either the 17- or 3-characteristic functional groups of DHT with SHBG. The association constants (K(a)1) for the binding of these immobilized DHT derivatives to the first binding site of SHBG, determined by SPR measurements, were 0.16 x 10(7) M(-1) for 17alpha-aminopropyl-17beta-hydroxy-5alpha-androstan-3-one (1), 1.64 x 10(7) M(-1) for 17alpha-aminocaproyl-17beta-hydroxy-5alpha-androstan-3-one (2), and 1.2 x 10(8) M(-1) for 1alpha-aminohexyl-17beta-hydroxy-5alpha-androstan-3-one (3). These values were compared with global K(a) data for the corresponding nonimmobilized DHT derivatives from equilibrium measurements using competitions with a tritiated testosterone tracer: the K(a) values were 1.25 x 10(7) M(-1) for 1, 1.50 x 10(7) M(-1) for 2, and 140 x 10(7) M(-1) for 3, confirming a remarkably high binding affinity of this latter compound for SHBG. A global fitting analysis of the biosensor data revealed that the interaction of the three immobilized steroids with SHBG was best described by a kinetic model assuming two structurally independent binding sites. This hypothesis of a bivalent binding model was also directly suggested by a dual fluorescent signal observed by the flow cytometry analysis of SHBG immobilized as a hybrid complex binding simultaneously two 1alpha-aminohexyl DHT ligands, one formed by 3, covalently coupled to phycoerythrin-labeled latex microspheres, and the other by the same DHT derivative, coupled to a fluorescein derivative (4).
PMID: 14622020 [PubMed - indexed for MEDLINE]
1: Brain Res. 2002 Sep 6;948(1-2):102-7. Related Articles, Links
Sex hormone binding globulin facilitates female sexual receptivity except when coupled to dihydrotestosterone.
Caldwell JD, Hofle S, Englof I.
Department of Biomedical Sciences, University of Illinois College of Medicine, 1601 Parkview Avenue, Rockford, IL 61107-1897, USA.
[email protected]
Sex hormone binding globulin (SHBG) is produced in brain where it is often co-localized with oxytocin. Infusions of SHBG into the medial preoptic area-anterior hypothalamus facilitate female sexual receptivity. SHBG has receptors on plasma membranes of the prostate gland where binding of the 5alpha-reduced androgen dihydrotestosterone (DHT) by SHBG acts as an antagonist on SHBG receptors. This study attempted to determine whether pre-coupling DHT to SHBG would inhibit SHBG-induced facilitation of female sexual receptivity. Ovariectomized rats were injected daily with 0.75 microg estradiol benzoate for 3 days. On the fourth day after a pre-infusion baseline behavioral test animals were infused with 1 microl per side through bilateral cannulae with SHBG (1.77x10(-6) M), SHBG coupled to DHT (SHBG-DHT; 1.66x10(-6) M DHT), with DHT alone or with artificial cerebrospinal fluid vehicle. As before, SHBG significantly increased female sexual receptivity when infused into the medial preoptic area-anterior hypothalamus. Rats infused with SHBG-DHT had significantly lower sexual receptivity. Therefore, whereas SHBG in the medial preoptic area facilitated female sexual behavior, SHBG coupled to DHT did not. DHT itself did not significantly affect sexual receptivity. Pre-coupling DHT to SHBG eliminated the facilitative effect of SHBG on female sexual receptivity just as DHT inhibits SHBG activity at prostate SHBG receptors suggesting that central receptors for SHBG are similar to those demonstrated in the periphery. Copyright 2002 Elsevier Science B.V.
PMID: 12383960 [PubMed - indexed for MEDLINE]
