Androgen production by testes of Gallus domesticus during postembryonic development.
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The effectiveness of steroids and gonadotropins (GtHs) in inducing final oocyte maturation was examined at different times of the day (0100, 0500, 0700, 0900, 1100, 1300, 1700, 2100 hr) in a daily spawning marine teleost, the tobinumeri-dragonet, Repomucenus beniteguri. The responsiveness of oocytes to GtHs and steroids was different at various times of day. The sensitivity of oocytes to hormones was apparent only during a certain period of the day (0100-0900 hr). Germinal vesicle breakdown (GVBD) could be induced by GtHs but not by steroids at 0100 hr. At 0500 hr, not only GtHs but also steroids at higher doses induced GVBD and ovulation. Oocytes underwent GVBD and ovulation at low doses of steroids at 0900 hr. GVBD and ovulation spontaneously occurred at 1100 and 1300 hr without any hormonal treatment. In addition, diameter and histological changes of ovarian oocytes were investigated. Ovarian oocytes were smaller than 420 microns, and only one oocyte group existed in distribution of oocyte frequency at 2100 and 0100 hr. With the increase in size of oocytes, two distinct groups appeared at 0500 hr. Larger oocytes completed GVBD at 1100 hr. Ovulation occurred between 1300 and 1700 hr and oviposition was completed between 1700 and 2100 hr daily. These results clearly show that the oocyte of the dragonet possesses a daily maturation rhythm. Responsiveness of oocytes to GtHs appeared earlier than responsiveness to steroids. This suggests that sensitivity to steroids is induced by GtH.
Somatic cells (interstitial cells and Sertoli cells) were prepared either as single cells or in clusters, from spermatogenic and mature trout testes, according to Loir (1988), and cultured for 10-14 days. Sertoli cells are 3 beta-HSD negative when prepared from testes resuming spermatogenesis and from mature testes, but they are 3 beta-HSD positive in spermatogenic testes. Progesterone, 17 alpha-hydroxyprogesterone (17 alpha-OH-P), and free androgens are secreted by interstitial cells, 11-ketotestosterone (11KT) being the predominating steroid produced immediately after seeding. These cells also produce high levels of glucuronated androgens. At least in mature spermiating testes they do not secrete estradiol. After isolation, interstitial cells would lose most of their ability to secrete 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta-OH-P) but they would recover it later. Testicular spermatozoa, which convert 17 alpha-OH-P independently of s-GtH, constitute a second source of this progestagen. In addition, our results suggest that Sertoli cells could be able to secrete 17 alpha-OH-P and also progesterone. A possible participation of the intralobular production of the former progestagen to the local regulation of germ cell maturation is evoked.
The inhibitory effects of progesterone (P), 5 alpha-dihydroprogesterone (5 alpha-DHP), 17 alpha-hydroxyprogesterone (17-HP), and deoxycorticosterone (DOC) upon the rapid onset of maternal behavior induced during late pregnancy in primigravid rats by ovariectomy-hysterectomy (OH) were examined. Progesterone administration at a dosage of 5.0 mg oil vehicle daily (beginning on Day 17 and ending when the subject responded maternally to foster pups) significantly delayed by about 1.5 to 2.0 days the onset of maternal behavior. In contrast, P at dosages of either 1.0 or 2.5 mg daily, 5 alpha-DHP at 5.0 mg administered daily in either an oil or Tween-80 vehicle, 17-HP at 5.0 mg in oil daily, and DOC at dosages of either 5.0 or 10.0 mg in oil daily failed to effect the rapid onset of maternal behavior induced by ovariectomy-hysterectomy on Day 17 of pregnancy. These data suggest that during pregnancy the onset of maternal behavior is inhibited in a rather specific manner by progesterone.
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Ovarian cells of pregnant rats were cultured with synthetic progestins (R5020, R2323), dexamethasone and RU486. Progesterone and 20 alpha-hydroxy-pregn-4-en-3-one (20 alpha-dihydroprogesterone) in the medium were measured by specific radioimmunoassay. Both R5020 and R2323 increased concentrations of these intrinsic progestins. RU486 decreased concentrations of progesterone, however, the addition of R5020 or R2323 counteracted this action. Immature hypophysectomized rats treated with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG) were administered with RU486; the serum levels of progesterone and 20 alpha-dihydroprogesterone tended to decrease. R5020 and R2323 inhibited the effect of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), whereas RU486 did not. Inhibition of the cholesterol side chain cleavage enzyme (CSCC) by RU486 was more marked than that by R5020 or R2323. These results show that RU486 decreases progesterone synthesis in cultured ovarian cells. A part of the mechanism may involve an inhibition of CSCC.
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A technique of incubation of testicular tissue in vitro with radiolabeled precursors was applied in the investigation of the steroid biosynthesis by testes of four young men after long-term, high-dose estrogen treatment. A positive correlation between plasma and testicular steroid levels, and in vitro capacity of the testes to metabolize progesterone was demonstrated. Estrogen administration produced a very significant inhibition of plasma and testicular levels of testosterone. The in vitro synthesis of testosterone from progesterone was very severely impaired; especially 17alpha-hydroxylation of progesterone. 20alpha-hydroxysteroid-dehydrogenase activity was found to be increased after estrogen treatment, both in vivo and in vitro. These findings suggest that testicular 17alpha-hydroxylase activity (and possibly also 17-20 lyase activity) is either under gonadotropin regulation, or is directly suppressed by estrogen. This could result by decreased enzyme synthesis, direct enzyme inhibition or affectation of the cofactors or cytochromes necessary for the enzymatic activity. 20alpha-reduction of C21-steroids would represent an alternative pathway for their catabolism, not regulated by gonadotropin or not affected by estrogen, that would be significant in situations with reduced 17alpha-hydroxylase activity.
Two novel microbial steroid hydroxylations were found in a screening of 131 microorganisms under aerobic conditions. 17 alpha-Hydroxyprogesterone was hydroxylated in the 8 beta-position by Corynespora melonis CBS 16260, and fermentation of 17 alpha-acetoxyprogesterone with Pycnosporium species ATCC 12231 yielded 11 beta-hydroxy- and 11 beta, 12 beta-dihydroxy-17 alpha-acetoxyprogesterone. The known 11 beta-hydroxy compound could be obtained as a single product with Trichothecium roseum ATCC 12519.
The serum levels of progesterone (delta4P), 20alpha-dihydroxyprogesterone (20alpha-DHP), pregnenolone (delta5P) and estrogens at different time intervals during Silastic-PVP-PGF2alpha tube induced midterm abortion were measured by radioimmunoassay in the rat and rabbit. The concentrations of delta4P and delta5P were significantly reduced but that of 20alpha-DHP was increased significantly as early as 20 hours after PGF2alpha treatment. Estrogen levels showed slight reduction in the rat but remained unchanged in the rabbit. The ratio of delta4P/20alpha-DHP recorded were 2.15 and 16.86 (pretreatment) and dropped to 0.08 and 0.37 (60 hours after insertion of Silastic-PVP-PGF2alpha tube) in the rat and rabbit, respectively. These findings suggest that the suppression of circulating delta4P by PGF2alpha might be the result of a reduced precursor (delta5P) pool size as well as changes in the enzymic systems responsible for the formation and conversion of delta4P. It is still to be determined if changes in estrogen levels in the rat have any bearing on abortion induced by PGF2alpha.
The effect of Trichosanthin (TCS), a protein obtained from the roots of Trichosanthis kirilowii, alone or in combination with prostaglandin-F2 alpha (PGF2 alpha; Tromethamine salt) on the termination of pregnancy in rabbits was investigated. Intraperitoneal injection of 1 or 2 mg TCS/10-day pregnant rabbits neither altered the serum progesterone (delta 4P) level nor interrupted pregnancy. Doses of 0.5 or 0.25 mg PGF2 alpha incorporated in a Silastic-PVP tube and inserted intravaginally, terminated pregnancy within 72 h of treatment in 75 and 16% of the treated does, respectively. By contrast, does treated on day-10 of pregnancy with a combination of a non-effective dose of TCS (1 mg) and a sub-effective dose of PGF2 alpha (0.25 mg) terminated pregnancy in all the treated animals as no live embryos were found within 3 days of treatment. Pregnancy interruption was associated with a significant reduction of serum delta 4P and delta 4P/20 alpha-dihydroprogesterone (20 alpha-DHP) ratio. The present study indicates that TCS and PGF2 alpha act synergistically, rendering the termination of 10-day pregnancy possible in the rabbit. It was also noted that pregnancy cannot be maintained when the serum delta 4 P level drops below 4 ng/ml and delta 4P/20 alpha-DHP falls lower than 0.6 in the 10-day pregnant rabbit.
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INTRODUCTION: This study compared two regimens of a monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (Perlutan) over 12 cycles of use. METHODS: Three hundred sixty-five adolescents were randomized into two groups. The patients in Group 1 received an initial injection of Perlutan on the 1st-5th day of their menstrual cycle and subsequent injections every 30 +/- 3 days, whereas those in Group 2 followed the traditional schedule of administration in which the first injection is administered between Days 7 and 10 of their menstrual cycle and subsequent injections 7-10 days after Day 1 of withdrawal bleeding. This schedule may result in an irregularity in the timing of injections. RESULTS: No significant difference was found between the two groups regarding tolerability or pregnancy (two in Group 1 and three in Group 2). CONCLUSION: Monthly administration limits the annual number of injections to a maximum of 12, thus frequently reducing the total annual dose while maintaining efficacy and tolerability similar to those obtained with the traditional regimen.
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