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The cytochrome P450-dependent liver monooxygenase system is influenced by many endocrine glands. The components of the system show circadian rhythmicity and therefore their activities change during the day. This may suggest that the pineal gland, whose activity is strongly related to the external environment, influences this metabolic system. A growing interest in melatonin used as a nonprescription drug that inhibits aging and cures various diseases prompted us to investigate the influence of pineal hormones on the liver's metabolic system. The aim of this study was to evaluate the effect of pinealectomy, melatonin, or serotonin on the cytochrome P450-dependent monooxygenase system. The experiment was performed on sexually mature male Wistar rats. The rats were divided as follows: a control group, pinealectomized rats, melatonin-treated rats, and seroto- nin-treated rats. Pinealectomy was done 14 days before decapitation. The isolated microsomal fraction was assayed for the activity of cytochrome P450-dependent monooxygenase system and for the activity of the enzymatic system, which non-obligatorily cooperates with the MFO system. Both pinealectomy and prolonged administration of melatonin or serotonin modified the activity of the mixed function oxidase system. In all experimental groups the components of microsome electron-transport chain I were inhibited. In microsome electron-transport chain II only melatonin and serotonin produced an inhibitory effect, while pinealectomy did not affect cytochrome b5 and NADH-cytochrome b5 reductase. 4-Aminopyrine N-deme- thylase and aniline hydroxylase did not alter either after pinealectomy or melatonin treatment (only a decreasing tendency was noted). In contrast, serotonin treatment decreased these activities significantly.
Progesterone (P4), which is produced by the corpus luteum (CL), creates proper conditions for the embryo implantation, its development, and ensures proper conditions for the duration of pregnancy. Besides the non-genomic activity of P4 on target cells, its main physiological effect is caused through genomic action by the progesterone nuclear receptor (PGR). This nuclear progesterone receptor occurs in two specific isoforms, PGRA and PGRB. PGRA isoform acts as an inhibitor of transcriptional action of PGRB. The inactive receptor is connected with chaperone proteins and attachment of P4 causes disconnection of chaperones and unveiling of DNA binding domain (DBD). After receptor dimerization in the cells’ nucleus and interaction with hormone response element (HRE), the receptor coactivators are connected and transcription is initiated. The ratio of these isoforms changes during the estrous cycle and reflects the different levels of P4 effect on the reproductive system. Both isoforms, PGRA and PGRB, also show a different response to the P4 receptor antagonist activity. Connection of the antagonist to PGRA can block PGRB, but acting through the PGRB isoform, P4 receptor antagonist may undergo conversion to a strongly receptor agonist. A third isoform, PGRC, has also been revealed. This isoform is the shortest and does not have transcriptional activity. Alternative splicing and insertion of additional exons may lead to the formation of different PGR isoforms. This paper summarizes the available data on the progesterone receptor isoforms and its regulatory action within the female reproductive system.
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