Administration of different steroid hormones in vivo has distinct and specific effects on the MAO activity of the adrenal medulla. In an effort to reconstitute these effects in defined cells, we have isolated endothelial cells and chromaffin cells from the bovine adrenal medulla and tested each cell type for sensitivity to these steroids. As in the intact animal, we found that endothelial cell MAO activity was stimulated 1.5- 2.5-fold by 10 microM progesterone, hydrocortisone, and dexamethasone, inhibited by ca. 50% by 17-alpha-estradiol, but unaffected by testosterone. The type of MAO in the endothelial cells was found to be exclusively of the A type. The chromaffin cells had MAO B exclusively and were inert to treatment with dexamethasone. The mode of action of the various steroids on MAO A activity in endothelial cells seemed to be that of affecting the number of MAO molecules, as binding of [3H]pargyline, an MAO inhibitor, changed in proportion to changes in enzyme activity. Consistently, the kinetic parameters for MAO A showed changes in Vmax but not Km under all conditions. The specificity of steroid action on MAO A activity was also supported by the fact that steroid-induced changes in total cell division ([14C]thymidine incorporation) and total protein synthesis ([14C]leucine incorporation) were seen after changes in MAO A. We conclude that the differential effects of steroids on MAO activity in the intact adrenal medulla can be reproduced in cultured adrenal medullary endothelial cells but not in chromaffin cells. Therefore we suggest that the action of these steroid hormones on the intact adrenal medulla may be restricted to the endothelial cell component of this tissue.

Introduction A popular treatment choice for male hypogonadism is topical testosterone gel. Two proprietary formulations, Testim Gel 1% (Auxilium Pharmaceuticals, Malvern, PA, USA) and AndroGel 1% (Solvay Pharmaceuticals, Marietta, GA, USA), are available. The recommended Testim application site is limited to the arms/shoulders, whereas AndroGel may be applied to the abdomen, shoulders, and upper arms. Aim To compare absorption variability when applying Testim to various body sites. Main Outcome Measures Total testosterone (TT) and calculated free testosterone (CTfree). Methods Hypogonadal men (TT < 300 ng/mL) applied Testim to three distinct anatomical sites for 1 month per site: arms/shoulders (A), chest/abdomen (C), and calves/legs (L). Pretreatment TT and CTfree were compared with end-of-month measurements. Safety was assessed with prostate-specific antigen (PSA) and hemoglobin (Hb) measurements. Results Twenty-one hypogonadal men (age 56.9 ± 9.0) naïve to prior testosterone therapy and otherwise in good health participated. Three groups of seven applied Testim in the sequence ACL, CLA, and LAC. Overall TT and CTfree increased significantly over pretreatment levels (P < 0.0001) into the normal range. Application sites differed with regard to TT levels achieved, A > C ≥ L (P = 0.011). No significant sequence effects were observed, however, the ACL group achieved the highest levels. CTfree correlated well with TT in all men (R2 = 0.87) and by application site (R2 = 0.91, 0.85, and 0.86 for A, C, L, respectively). Pre- and post-treatment PSAs were similar; mean pretreatment Hb increased from 14.7 ± 1.47 to 15.5 ± 1.3 g/dL at month 3. Hemoglobin corrected to normal in four subjects with anemia at enrollment (Hb < 13.5 g/dL). Conclusions Testim Gel 1% applied to various anatomical sites increases TT and CTfree into the normal range; the best levels are achieved with arms/shoulder application. Flexibility in the application site of Testim is possible if TT or CTfree is monitored to ensure adequate therapeutic levels. Anemia, possibly associated with testosterone deficiency, was an incidental finding in several men and was corrected with topical testosterone replacement.

No abstract

No abstract