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Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/ peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20-73 yr, BMI 21-32 kg/[m.sup.2], participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion (P = 0.003), 2) potentiated the agerelated abbreviation of LH secretory bursts (P = 0.025), 3) suppressed incremental GnRH-induced LH release (P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release (P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH (P = 0.002) and T (P = 0.017) concentrations, 2) accelerating LH pulse frequency (P = 0.013), 3) amplifying total (basal plus pulsatile) LH (P = 0.002) and T (P < 0.001) secretion, 4) shortening LH secretory bursts (P = 0.032), and 5) reducing LH secretory regularity (P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion (P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men. leuteinizing hormone; testosterone; pulsatile; secretion; human; approximate entropy doi: 10.1152/ajpendo.00300.2010.

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg x [kg.sup.-1] x [day.sup.-1]) for 1 wk. Baseline blood pressures were similar between growthrestricted (112 [+ or -] 3 mmHg) and control (110 [+ or -] 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng x [kg.sup.-1] x [min.sup.-1] for 30 min) was observed in growth-restricted (160 [+ or -] 2 mmHg) vs. control (136 [+ or -] 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 [+ or -] 2 mmHg) rats with no significant effect on blood pressure in controls (130 [+ or -] 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 [micro]g/min) in control (184 [+ or -] 5 mmHg) and growth-restricted (184 [+ or -] 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR. sex steroids; blood pressure; developmental programming doi: 10.1152/ajpregu.00096.2010.

Introduction The small heterodimer partner (Shp; referred to herein as Nr0b2) is mainly known for its role in the liver, where it is involved in the feedback inhibition of bile [...], Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen diethylstilbestrol (DES). Although the molecular basis for this effect remains unknown, estrogen receptors likely play a critical role in mediating DES-induced infertility. Recently, we showed that the orphan nuclear receptor small heterodimer partner (Nr0b2), which is both a target gene and a transcriptional repressor of estrogen receptors, controls testicular function by regulating germ cell entry into meiosis and testosterone synthesis. We therefore hypothesized that some of the harmful effects of DES on testes could be mediated through Nr0b2. Here, we present data demonstrating that Nr0b2 deficiency protected mice against the negative effects of DES on testis development and function. During postnatal development, Nr0b2-null mice were resistant to DES-mediated inhibition of germ cell differentiation, which maybe the result of interference by Nr0b2 with retinoid signals that control meiosis. Adult Nr0b2-null male mice were also protected against the effects of DES; however, we suggest that this phenomenon was due to the removal of the repressive effects of Nr0b2 on steroidogenesis. Together, these data demonstrate that Nr0b2 plays a critical role in the pathophysiological changes induced by DES in the mouse testis.

Using a commercially available testosterone enzyme immunoassay (EIA), we developed and validated an assay procedure for determining testosterone levels in small-volume (20 [micro]L) avian plasma samples. We evaluated this EIA's utility by measuring plasma testosterone levels in Mourning Doves (Zenaida macroura), White-eyed Vireos (Vireo griseus), Red-eyed Vireos (Vireo olivaceus), and Indigo Buntings (Passerina cyanea). Standard biochemical validations (e.g., parallelism, recovery of exogenous testosterone) demonstrated that the assay accurately and precisely measured testosterone in avian plasma. We compared plasma testosterone levels in males and females of all four species and Indigo Buntings in various reproductive stages to physiologically validate the assay's ability to determine biologically important changes in testosterone levels. Plasma testosterone levels were higher in males compared to females in three of four species. Prebreeding and breeding male Indigo Buntings had higher circulating testosterone levels than postbreeding males. Testosterone levels in our study were similar to reported values for other passerine species using radioimmunoassay procedures. Our results suggest that this EIA procedure is very effective for determining testosterone levels in small-volume avian plasma samples and is sensitive enough to detect biologically important changes in the gonadal activity of birds. Thus, this assay has considerable utility for measuring testosterone in small birds ( Key words: Columbiformes, enzyme immunoassay, Passeriformes, plasma, testosterone. Empleando un inmunoensayo enzimatico de testosterona disponible comercialmente, desarrollamos y validamos un procedimiento para determinar los niveles de testosterona en volumenes pequenos (20 [micro]L) de muestras de plasma de aves. Evaluamos la utilidad de este procedimiento midiendo los niveles plasmaticos de testosterona en Zenaida macroura, Vireo griseus, Vireo olivaceus y Passerina cyanea. Validaciones bioquimicas estandar (e.g., paralelismo, recuperacion de testosterona exogena) demostraron que el ensayo mide la testosterona plasmatica con exactitud y precision. Para validar fisiologicamente la habilidad del ensayo para detectar cambios biologicamente importantes en los niveles de testosterona, comparamos los niveles plasmaticos de testosterona entre machos y hembras de las cuatro especies y entre varios estadios reproductivos de P. cyanea. Los niveles plasmaticos de testosterona fueron mayores en los machos que en las hembras en tres de las cuatro especies. Los individuos pre-reproductivos y los machos reproductivos de P. cyanea presentaron niveles circulantes de testosterona mayores que los machos post-reproductivos. Los niveles de testosterona documentados por nuestro estudio fueron similares a los reportados para otras especies de aves paserinas mediante radioinmunoensayos. Nuestros resultados sugieren que el inmunoensayo enzimatico de testosterona es un procedimiento muy efectivo para determinar los niveles de testosterona en las aves a partir de muestras de plasma de volumen pequeno, y que este es lo suficientemente sensible como para detectar cambios biologicamente importantes en la actividad de las gonadas de las aves. Por lo tanto, este ensayo presenta una utilidad considerable para medir la testosterona en aves pequenas (

The objective of this project was to characterize changes in growth, carcass yield, and meat quality traits in castrates and gilts in response to divergent selection for testosterone production. In generation 21, endogenous testosterone concentrations in Duroc boars of the high (HTL) and low (LTL) testosterone lines averaged 49.0 and 27.8 ng/mL (P < 0.01), respectively. Eight LTL and 10 HTL boars were used to sire 29 LTL and 33 HTL litters. To remove the effects of inbreeding, these same boars were mated to females of a Large White x Landrace composite (WC) to generate 11 WC by LTL litters (WLT) and 23 WC by HTL litters (WHT). Castrates and gilts were then allotted to LTL (n = 53), HTL (n = 61), WLT (n = 102), and WHT (n = 101) for testing. Growth and carcass traits analyzed included days to 114 kg (D114), ADG, backfat adjusted to 114 kg (ABF), LM area adjusted to 114 kg and predicted percent lean (PPL). Fat-O-Meater data collected were adjusted fat depth (AFD), adjusted loin depth, and percent lean. Meat quality traits characterized at 24 h postmortem included marbling score, percent lipid, pH, drip loss, color score, and Minolta [L.sup.*], [a.sup.*], and [b.sup.*]. Data were analyzed with a mixed model including fixed effects of line, mating type (purebred or crossbred), sex, and the random effect of sire nested within line. All possible interactions among fixed effects were tested. The HTL had fewer D114 (P < 0.05), greater ADG (P < 0.01), greater ABF (P < 0.01), and lower PPL (P < 0.01) than LTL. The WHT and WLT did not differ for D114, ADG, or ABF. The WHT had smaller LM area adjusted to 114 kg (P < 0.05) and greater drip loss (P < 0.05) than WLT. The WLT had lower adjusted loin depth (P < 0.05) than LTL and HTL. The LTL and HTL had greater subjective scores for marbling (P < 0.05) compared with WLT and WHT. The least squares mean for percent lipid for HTL and LTL was 4.00. The WHT had greater means for [L.sup.*], [a.sup.*], and [b.sup.*] (P < 0.05) than WLT. Pigs selected for increased testosterone production grew faster and produced fatter carcasses than pigs selected for decreased testosterone. Changes in growth, carcass yield, and meat quality traits were detected in castrates and gilts in response to divergent selection for testosterone production. Key words: growth, meat quality, pig, testosterone

The objective of the present study was to evaluate the secretion of testosterone (T) in bulls in response to the administration of varying doses of bovine LH (bLH) during the four seasons of the year. Five adult bulls (4 yr of age) were treated with an amount of bLH that was estimated to induce a 5 ng/mL amplitude pulse of LH in blood serum on five consecutive days around the spring equinox, summer solstice, fall equinox, and winter solstice. Five hours after this dose, bulls were treated with bLH in amounts that were estimated to induce a 0.25, 0.5, 1, 2, or 4 ng/mL amplitude LH pulse in blood serum in a Latin square design. Blood samples were collected for 5 h after administration of a dose of bLH that was estimated to induce the 5-ng amplitude LH pulse, and for 3 h after administration of the variable doses of bLH, and were then assayed for concentrations of T. Average concentrations and amplitude of T release after doses of bLH that were estimated to induce the 5-ng amplitude LH pulses were greater during the spring and summer than during the winter (P < 0.05). The area under the release curve (AUC) was greater during the spring than during the winter (P < 0.05). During the 3 h after treatment with the variable doses of bLH, T response was affected by dose (P < 0.001) and season (P < 0.001), but there was no dose x season interaction. Testosterone response increased in a dose-dependent fashion for all variables studied. The greatest average concentrations of T and AUC were observed in the spring compared with the fall and winter (P < 0.05). These data support our working hypothesis that testes of bulls are more responsive in releasing T in response to bLH stimulation in the spring and summer compared with the winter; however, there were no changes in sensitivity of the testes to LH during different seasons of the year as indicated by the lack of a dose of bLH x season interaction. Key Words: Cattle, Male Animals, Seasonal Variation, Testes, Testosterone

Keywords: dihydrotestosterone, steroid 5α-reductase, sexual differentiation, hormone action, male pseudohermaphroditism, Autobiography Abstract My work in physiology was designed to investigate the process of androgen action within target cells and to use this information to provide insight into the clinical disorders of androgen action. The discovery that the circulating male androgen testosterone is 5α-reduced to a more potent hormone, dihydrotestosterone, in target tissues and that dihydrotestosterone and testosterone work by binding to the same androgen receptor protein has provided insight into the inherited syndromes of androgen resistance that impair the formation of the male urogenital tract during embryogenesis and into the role of continued dihydrotestosterone formation in the pathogenesis of prostatic hyperplasia in dogs and men.