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Biomedical subjects

J Weisz

Publications and source records attributed to J Weisz.

At least 91 records · Page 5Linked to original sources

Direct inhibition of tyrosine hydroxylase activity by catechol estrogens.

Catechol estrogens, the 2-hydroxylated metabolites of estrogens, recently shown to be formed in brain, inhibit tyrosine hydroxylase, the enzyme that catalyzes the pivotal step in the biosynthesis of the neurotransmitters dopamine and norepinephrine. The nature of the inhibition is by competition with the pterin cofactor and thus resembles feedback inhibition of the enzyme by catecholamines.

Animals↗

Methylation of estradiol-17 beta by a partially purified preparation of bovine pineal hydroxy-indole-O-methyltransferase.

A partially purified preparation of hydroxy-indole-O-methyltransferase (HIOMT) from bovine pineal was shown to O-methylate estradiol-17beta (E2). The HIOMT preparation was incubated with E2 and [3H]-S-adenosylmethionine (SAM). The [3H]-3 methyl-ether or estradiol [MeO-E2] produced was identified by thin layer chromatography (TLC) and crystallization to constant 3H/14C ratio in the presence of [14C]-MeO-E2 and unlabeled MeO-E2 standards. The kinetics of the enzyme reaction for melatonin formation from N-acetyl-serotonin (NAS) and for MeO-E2 were compared.

Acetylserotonin O-Methyltransferase↗

Identification of cytochrome P-450, and its distribution in the membrana granulosa of the preovulatory follicle, using quantitative cytochemistry.

The distribution of cytochrome P-450 (C-P450), an essential component of the oxidative enzyme system involved in the hydroxylation of steroids, was measured by quantitative cytochemistry in cryostat sections of preovulatory follicles obtained from rats in proestrous. The sections were reacted with medium saturated with carbon monoxide with or without the addition of sodium dithionite. The absorbance spectrum was measured from 400 to 500 nm and a difference spectrum calculated by subtracting the extinction obtained from incubations without sodium dithionite from that obtained in the presence of sodium dithionite. A distinct peak at 450nm was recorded in cells of the peripheral portion of the membrana granulosa (MG) but not in those of the cumulus, providing evidence for the presence and differential distribution of C-P450 in the MG of the preovulatory follicle.

Animals↗

Effects of testosterone and dihydrotestosterone on spermatogenesis, rete testis fluid, and peripheral androgen levels in hypophysectomized rats.

To compare the effects of testosterone (T) and dihydrotestosterone (DHT) on the maintenance and the restoration of spermatogenesis, hypophysectomized (APX) rats were treated daily for 35 days with 0.5 mg of T propionate (TP) or DHT propionate (DHTP) beginning 5 or 33 days after hypophysectomy. In the maintenance experiment, the weights of the testes and the number of early spermatids were significantly lower in DHTP-than in TP-treated animals, while late spermatids were present only in rats treated with TP. In the restoration experiment, TP increased testicular weight and the number of germinal cells, whereas DHTP had very little effect on the testis. In an attempt to explain these findings, we measured androgen levels in the rete testis fluid (RTF) and peripheral plasma of APX rats treated with TP or DHTP. The concentration of T in the RTF of TP-treated rats was nearly 3-fold higher than the level of DHT in the RTF of animals given DHTP. Plasma T levels measured 1/2, 2, 4, and 24 hours after the last of three daily injections of TP were considerably higher than were the corresponding plasma DHT levels in animals given DHTP. In animals treated with free steroids, peripheral androgen levels between 1/2 and 4 hours after the last injection were much higher in rats given T than in those given DHT, but thereafter this difference disappeared. We conclude that the difference in the ability of subcutaneously injected TP and DHTP to maintain and to restore spermatogenesis in APX rats was due to a difference in androgen levels in the testes of these animals.

Animals↗

Release of gonadotrophin-releasing hormone (Gn-RH) from isolated, perifused medial-basal hypothalamus by melatonin.

Basal release of Gn-RH from perifused medial-basal hypothalami of rats was at or below levels detectable by radioimmunoassay. Infusion of norepinephrine, dopamine, acetylcholine or serotonin (0.1-10 mM) as 10-20 min pulses was not associated with a detectable increase of Gn-RH in the effluent. However, 10-20 min pulses of melatonin (0.1-1.0 mM) consistently caused release of Gn-RH.

Acetylcholine↗

Patterns of LH and FSH release from perifused rat pituitaries in response to infusions of hypothalamic extract.

A continuous flow incubation (perufusion) system was developed in which the secretory responses of pools of hemipituitaries from adult male rats to hypothalamic extract (HE) were characterized by serial radioimmunoassay of LH and FSH in the effluent medium. There was in initial massive release of LH and FSH which, in the absence of HE, declined to low basal levels at a rate which depended on the flow rate. Thereafter, the baseline for LH continued to decline gradually while that for FSH was stable. The rate of LH and FSH release rose abruptly after addition of the HE to the medium and returned promptly to baseline after withdrawal of the HE. During continuous infusion of HE for five hours, LH secretion was maintained at a relatively constant, elevated level. The responses to repeated identical pulses of HE were highly reproducible. The variability between responses by any one pool of tissue was significantly less than between responses of separate pituitary pools including pools comprising right and left halves of the same glands. For any given pool of pituitaries of the relationships were linear between: 1) duration of HE pulses (concentration constant) and increases in LH output, and 2) log of concentration of HE (pulse duration constant) and increases inLH and in FSH output. Consistent responses were obtained for up to 12 hr, the maximum period tested.

Animals↗

Direct effect of testosterone and its 5alpha-reduced metabolites on pituitary LH and FSH release in vitro: change in pituitary responsiveness to hypothalamic extract.

A continuous flow incubation (perifusion) system was used to examine the effect of testosterone (T) and three of its 5alpha-reduced metabolites, dihydrotestosterone (DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-Adiol) and its 3beta-epimer (3beta-Adiol) on LH and FSH release, induced by hypothalamic extract (HE). In the absence of steroids, successive identical pulses of HE, of 10 min duration each, administered at hourly intervals over a 8-hr period, caused highly reproducible release of LH and FSH. In experimental perifusions, the amounts of LH and FSH released in response to standard 10-min pulses of HE administered at hourly intervals during the continuous infusion of steroid for 4-6 hr were compared with the responses of the same pituitaries to the standard test pulses of HE given before the start of the steroid infusion and after its cessation. All the androgens tested altered pituitary responsiveness. At the 0.1 and 1.0 mug/ml dose level there were differences between the steroids in the way they influenced the responsiveness of the pituitary overtime. Their effects at these two doses fell into three categories depending on whether there was initially: 1) an augmentation of HE induced LH release (T and 3beta-Adiol), 2) augmentation of both FSH and LH release (DHT), OR 3) NO AUGMENTATION IN THE RELEASE OF EITHer gonadotrophin (3alpha-Adiol). All the androgens ultimately suppressed pituitary responsiveness to HE and all were associated with changes in the ratios of LH and FSH released. When the dose of T and 3 beta-Adiol was raised to 10 mug/ml or that of DHT lowered to 0.01 mug/ml the initial stimulatory phase was not seen. Epitestosterone, the biologically inactive epimer of T, did not alter the responsiveness of the pituitary of HE.

Androstanes↗