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S A Daniel

Publications and source records attributed to S A Daniel.

25 records · Page 2Linked to original sources

Androgen inhibition of FSH-stimulated progesterone production by granulosa cells of prepubertal pigs.

Androgens have been reported to stimulate progesterone production by granulosa cells of several species, and to act synergistically with FSH in stimulation of progesterone accumulation by rat granulosa cells. Studies were undertaken to examine the effect of androgens on FSH-stimulated progesterone production in culture by granulosa cells derived from prepubertal pig ovaries. When included in 24-h culture with FSH, both androstenedione and testosterone caused a reduction in progesterone accumulation, but dihydrotestosterone and androsterone did not. Granulosa cells were cultured for 24 h with FSH and [14C]progesterone with or without testosterone; testosterone did not affect the rate of overall metabolism of [14C]progesterone and it was therefore concluded that testosterone inhibited progesterone synthesis, rather than enhancing its catabolism. 17 beta-Estradiol also inhibited FSH-stimulated progesterone accumulation. To determine whether the action of testosterone was mediated by conversion to estradiol, granulosa cells were cultured with FSH and testosterone with or without an aromatase inhibitor (4-acetoxy-androstenedione). The aromatase inhibitor failed to prevent the testosterone-induced reduction in progesterone accumulation, although it markedly inhibited estradiol accumulation. These results indicate that theca-derived androgens can inhibit FSH-stimulated progesterone production by granulosa cells in the prepubertal pig, independently of estradiol.

Androgens↗

Site of action of androgens on follicle-stimulating hormone-induced aromatase activity in cultured rat granulosa cells.

This paper describes experiments on cultured granulosa cells isolated from ovaries of immature rats designed to locate the site of action of androgens on FSH-induced aromatase activity. Treatment of cells during a 36-h induction period with (Bu)2cAMP, 8- BrcAMP , FSH, prostaglandin E2, or cholera toxin resulted in induction of aromatase activity measured as 17 beta-estradiol accumulation during a 6-h test period with testosterone (5 X 10(-7) M) added to medium as substrate. Presence of testosterone (5 X 10(-7) M) during the induction period enhanced the effects of FSH, cholera toxin, and prostaglandin E2 on aromatase activity, but not those of the cAMP analogs. The effects of culturing and steroids on responsiveness of granulosa cells to FSH (measured as FSH-stimulated cAMP production during a 1-h test period) were examined. The data showed that culturing in medium alone for 36 h resulted in a decrease in the ability of FSH to stimulate cAMP production when compared to that of freshly isolated cells. After culture with testosterone (5 X 10(-7) M), dihydrotestosterone (DHT) (5 X 10(-7) M), or 17 beta-estradiol (5 X 10(-7) M), responsiveness was at least partially restored. After treatment with progesterone (5 X 10(-7) M), FSH stimulation of cAMP production was not significantly different from that of cells cultured in medium alone. Hydroxyflutamide (5 X 10(-5) M), an antiandrogen known to block androgen-receptor interaction, abolished the effect of DHT and depressed the effect of testosterone on responsiveness of granulosa cells to FSH. Cells treated for 36 h with testosterone (5 X 10(-7) M) bound significantly more [125I]iodo-FSH than cells cultured in medium alone. Although DHT (5 X 10(-7) M) slightly increased FSH binding, the effect was not statistically significant. These results suggested that androgens regulate granulosa cell aromatase activity not only as substrates, but also by acting at a site before cAMP production (possibly at the level of the FSH receptor) in the control of FSH-induced enzyme activity.

8-Bromo Cyclic Adenosine Monophosphate↗

Involvement of estrogens in the regulation of granulosa cell aromatase activity.

Androgens have been shown to enhance follicle-stimulating hormones (FSH) induced aromatase activity in cultured granulosa cells obtained from the ovaries of immature rats, however, aromatizable androgens are more effective than nonaromatizable androgens. The present study was designed to investigate the possibility that aromatization of androgens to estrogens is responsible for the greater effectiveness of aromatizable androgens. Granulosa cells were cultured during a 36-h induction period in the presence of FSH, FSH + testosterone, or FSH + dihydrotestosterone with or without 4-acetoxy-4-androstene-3,17-dione (4-acetoxy-A), an inhibitor of aromatase activity. Treatment with androgens enhanced aromatase activity measured as accumulation of estradiol-17 beta during a 6-h test period with testosterone added as substrate. The effects of both androgens on FSH-induced aromatase activity were blocked by 4-acetoxy-A. Presence of a high concentration of diethylstilbestrol (DES), a synthetic estrogen, during the induction period had a significant positive effect on FSH-induced estradiol-17 beta accumulation during the test period. All lower doses were ineffective. Nafoxidine, an antiestrogen known to inhibit binding of estrogens to their intracellular receptors, had no effect on enhancement of FSH-induced aromatase by testosterone. The results of these experiments suggest that estrogens synthesized by granulosa cells in culture are only partially responsible for the greater ability of testosterone to enhance FSH-induced aromatase activity compared with that of dihydrotestosterone (DHT). Other factors such as differential rates of androgen metabolism and receptor affinities are probably the major determinants of androgen potency.

Androstenedione↗

Methadone-induced attenuation of the effects of delta 9-tetrahydrocannabinol on temporal discrimination in pigeons.

Pigeons responded under a discrete trial procedure in which they were required to peck one of two keys depending on the duration of a conditional stimulus (general illumination of the experimental chamber). Correct choices (red key after a 4-sec stimulus; green key after an 8-sec stimulus) resulted in the intermittent presentation of food; incorrect choices resulted in a darkened chamber. Intermediate durations (probe stimuli) were also presented occasionally. The effects of tetrahydrocannabinol (THC; 0.06-0.50 mg/kg) and repeated methadone injections (2-20 mg/kg/day) were assessed alone and in combination. THC resulted in a dose-dependent decrease in accuracy with the greater effect on long-duration trials. Repeated methadone alone resulted in a decrease in accuracy only when the methadone dose was changed. High doses of methadone (6 and 20 mg/kg/day) resulted in either a complete (0.25 mg/kg of THC) or partial (0.50 mg/kg of THC) attenuation of effects of THC on temporal discrimination accuracy as compared to a low methadone dose (2 mg/kg/day) or THC alone. The results suggest the possibility of cross-tolerance or antagonism between methadone and THC.

Animals↗

Reversal learning tasks may provide rapid determination of cognitive deficits in lead-exposed children.

An historical cohort study of twins, aged 6 to 15 years, found reduced cognitive performance related to subclinical exposure to lead (Pb) much earlier in life. Pairs of twins discordant for blood Pb (low-Pb twins ranged from 30-50 micrograms/dl and high-Pb twins ranged from 43-80 micrograms/dl) exhibited reduced learning of a computer-administered visual discrimination and reversal by the twin having the higher exposure. There was no evidence that sensory or motor impairment contributed to the cognitive deficit. Performance of a reference group indicated that test's validity for age-related cognitive development and the method's suitability for children of varying socio-economic or racial status. Because the reversal learning approach required only one 20-min test session and was powerful enough to document Pb-related deficits in a small sample (n = 8), it may indicate a practical method for obtaining early evidence of environmentally induced developmental delays. An advantage of the test is that it can be used with both humans and animals. Tests capable of direct comparison of behavioral data from humans and animals can guide the search for behavioral and biological mechanisms in experiments that can be done only with animals. They also can augment the clinical procedures currently used.

Adolescent↗

Effects of acrylamide on multiple behavioral endpoints in the pigeon.

Little is known about acrylamide's effects on cognitive function in animals. Twelve pigeons were trained to stable levels of performance. We then determined the effects of subchronic exposure (p.o.) of 0, 20, and 60 mg/kg/day of acrylamide monomer on (1) duration discrimination responding; (2) fixed-interval performance; and (3) shape discrimination responding. Sixty mg/kg/day caused rapid impairment on all tests; recovery of various endpoints varied from 2 or 3 days to more than 4 weeks. Response latency recovered much more rapidly than the accuracy of duration discrimination. Measures of responding and discrimination recovered at approximately the same time for the FI and shape discrimination. FI response rate remained elevated post-acrylamide. Administration of 20 mg/kg/day for 90 days produced a consistent, but not significant, decrease in the accuracy of duration discrimination. Acrylamide affects a variety of behavioral processes involving sensory, motor and associative functions.

Acrylamide↗