Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have earlier reported that dopamine (DA) activity in the preoptic anterior hypothalamic (POA-AH) region of castrated rats is inhibited by testosterone and accelerated by PRL. These results suggested that dopaminergic neurons may play an important role in male copulatory behavior, particularly in the attenuation of sex behavior reported to be associated with hyperprolactinemia. We have now examined the effects of severe hyperprolactinemia on the POA-AH DA activity in association with any modifications of copulatory behavior. Sexually experienced adult male rats were castrated and implanted sc with Silastic implants containing testosterone to maintain serum testosterone levels in the range found in intact rats. Hyperprolactinemia was induced by inoculation of minced MtTW15 PRL secreting pituitary tumor fragments. Copulatory behavior was assessed at weekly intervals in hyperprolactinemic and control rats. During the period of tumor growth serum PRL levels increased logarithmically. Whereas sexual activity continued to improve in control rats, there was a marked decrease in several important parameters of copulatory behavior in hyperprolactinemic rats. The most dramatic decrease occurred in the percentage of tumor-bearing rats ejaculating which decreased progressively to zero at 6 weeks after tumor inoculation. Ejaculation frequency decreased and ejaculation latency increased in tumor-bearing rats before the complete disappearance of ejaculatory behavior. The deficits in copulatory behavior of hyperprolactinemic rats were accompanied in parallel studies by significant depletions of DA concentrations in the POA-AH. Further, neuronal activity, as evidenced by the turnover rates measured by rate of loss of DA after tyrosine hydroxylase inhibition with alpha-methyl paratyrosine, was markedly augmented in the POA-AH of hyperprolactinemic rats as compared to control animals. These findings disclose a close association between the acceleration in POA-AH DA activity and the attenuation of copulatory behavior induced by hyperprolactinemia and suggest the probability of an underlying role of the POA-AH DA neurons in male sex behavior normally induced by testosterone.
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PMID:Effects on male sex behavior and preoptic dopamine neurons of hyperprolactinemia induced by MtTW15 pituitary tumors. 664 26

Previous studies have used recombinant retroviruses encoding the tyrosine hydroxylase (TH) gene to transduce various cell lines, including fibroblasts (NIH-3T3), a pituitary tumor cell line (AtT20), and a pancreatic endocrine line (RIN). These genetically modified cells, synthesizing either 3,4-dihydroxyphenylalanine, dopamine, or both, are potential donors for treatment of Parkinson's disease. However, the levels of TH protein in such transduced cells have been low and heterogeneous. Using several modified versions of retrovirus vectors encoding TH, we demonstrated that protein stability is an important factor governing levels of TH in NIH-3T3 fibroblasts. Whereas low levels of TH protein were observed in infected NIH-3T3 cells, high levels of a TH-beta gal fusion protein were found. This difference was due to a significantly longer half-life of the TH-beta gal fusion protein relative to TH alone. However, the TH-beta gal fusion protein was found to be enzymatically inactive. We also found that the half-life of the endogenous TH protein in PC-12 cells is sevenfold longer than the TH protein in transduced fibroblasts, implying that a cell-type specific regulator or mechanism may stabilize TH in catecholaminergic cells.
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PMID:The stability of endogenous tyrosine hydroxylase protein in PC-12 cells differs from that expressed in mouse fibroblasts by gene transfer. 750 76