ABSTRACT
OBJECTIVE: To evaluate the role of chronic long-term exogenous androgen administration to normal ovulatory women on adrenal steroidogenesis. DESIGN: Prospective study of four consecutive female-to-male transsexuals before and during chronic testosterone (T) therapy. SETTING: Clinical Research Center of the Mount Sinai Medical Center. PATIENTS: Four female-to-male transsexuals were studied before and during 6 to 12 months of chronic T enanthate therapy for desired virilization. All four subjects were ovulatory before treatment. Adrenocorticotropic hormone (ACTH) testing was performed before, and 6 and 12 months of androgen therapy and various adrenal androgens as well as precursor:product pairs were evaluated as an index of specific adrenocortical biosynthetic defects. RESULTS: Baseline and 1 hour after 0.25 mg ACTH intravenously, adrenal androgen levels as well as adrenal precursor/product pairs demonstrated no difference before and during chronic T treatment. Studies included determinations of plasma 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol. CONCLUSION: It is concluded that chronic hypertestosteronemia does not alter adrenal steroidogenesis.
Subject(s)
Adrenal Cortex Hormones/metabolism , Adrenal Cortex/metabolism , Androgens/pharmacology , Ovulation/physiology , 17-alpha-Hydroxypregnenolone/blood , Adrenal Cortex/drug effects , Adrenal Cortex/physiology , Adrenocorticotropic Hormone/administration & dosage , Adrenocorticotropic Hormone/pharmacology , Adult , Androgens/administration & dosage , Androstenedione/blood , Cortodoxone/blood , Dehydroepiandrosterone/blood , Dose-Response Relationship, Drug , Female , Humans , Hydrocortisone/blood , Injections, Intravenous , Middle Aged , Prospective Studies , Statistics as Topic , Testosterone/administration & dosage , Testosterone/pharmacology , TranssexualismABSTRACT
Arachidonic acid stimulated an increase in transmural electrical potential difference (p.d.) in guinea-pig seminal vesicle tissue in vitro. Pretreatment with indomethacin abolished this response. Indomethacin pretreatment did not prevent the p.d. from increasing in response to theophylline. Changes in p.d. in response to arachidonic acid were greatly attenuated, and the response to theophylline was abolished in seminal vesicle tissue taken from castrated guinea-pigs. Seminal vesicles, aorta and ileum taken from castrated guinea-pigs synthesized and released more prostaglandins than did those from control animals. It is concluded that the effects of arachidonic acid on p.d. are mediated by its metabolism to prostaglandins; the inability of seminal vesicles from castrated animals to respond to arachidonic acid is not a result of a decrease in prostaglandin production, but is more likely a result of other degenerative changes attendant upon castration; and androgens appear to have some regulatory function on prostaglandin synthesis in a variety of tissues.
Subject(s)
Prostaglandins/metabolism , Seminal Vesicles/physiology , Testis/physiology , Animals , Arachidonic Acid , Arachidonic Acids/metabolism , Arachidonic Acids/pharmacology , Guinea Pigs , In Vitro Techniques , Indomethacin/pharmacology , Male , Membrane Potentials , Prostaglandins/biosynthesis , Seminal Vesicles/drug effects , Theophylline/pharmacologyABSTRACT
The arachidonic acid lipoxygenase products released into culture supernatants by the human myeloid cell line K562 were quantitated by high-performance liquid chromatography. During 2 hr of incubation, K562 cells spontaneously released a mean of 9 ng of 15-monohydroxyeicosatetraenoic acid, 35 ng of 5-monohydroxyeicosatetraenoic acid, and 87 ng of a partially resolved mixture of 11- and 12-monohydroxyeicosatetraenoic acid per 10(7) cells. The addition of 50 micrograms of arachidonic acid per ml to the cell cultures increased the quantities of monohydroxyeicosatetraenoic acids generated after 2 hr of incubation by 10- to 100-fold; changes in the ratios of these lipoxygenase products occurred over 24 hr of incubation. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate, at concentrations of 5 to 25 ng/ml increased arachidonic acid lipoxygenation 1- to 2-fold in cultures containing 50 micrograms of arachidonic acid per ml, and up to 20-fold in cultures not supplemented with arachidonic acid. The lipoxygenation of arachidonic acid was enhanced 2- to 9-fold for up to 24 hr after a 2-hr exposure of K562 cells to 12-O-tetradecanoylphorbol-13-acetate. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked the effects of 12-O-tetradecanoylphorbol-13-acetate, suggesting that the monohydroxyeicosatetraenoic acids are the products of specific lipoxygenases rather than of nonenzymatic oxidative reactions. The capacities of phorbol esters to promote tumors in the mouse skin model corresponded to their respective capacities to enhance the lipoxygenation of arachidonic acid to 15- and 5-monohydroxyeico-satetraenoic acid but not to 11- and 12-monohydroxyeico-satetraenoic acid.
