The stimulated C-kinase activity in estradiol-treated rat pituitaries is reduced by chronic treatment with the dopamine agonist CV 205-502

Abstract

To investigate whether the modulation of lactotrope cell multiplication and prolactin secretion in rat pituitary glands implicated the phosphoinositide C-kinase system, female Wistar rats were treated or not with the dopamine agonist CV 205-502 or 8 days or with estradiol cervical implants for 8 for 15 days, alone or in combination with CV 205-502 for the last 8 days. CV 205-502 treatment induced a significant reduction in plasma PRL levels and in pituitary weights, whereas estradiol treatment induced a significant increase in both parameters.CV 205-502, in association with estradiol, counteracted estradiol stimulation of PRL levels and of pituitary weights. Total C-kinase activity in controls was 29.8 \ m=+-\ 9.9 pmol 32phosphorus/min (N = 7, mean \ m=+-\ sem), mainly found in the soluble fraction (84%). When administered alone, CV 205-502 induced a significant reduction (\p=n-\58%, p < 0.02) in C-kinase activity in the particulate fraction with no modification in the soluble fraction. Both 8 and 15 days estradiol treatment induced a significant stimulation of total C-kinase activity, 74% and 155% respectively. When combined with estradiol, CV 205-502 significantly (p < 0.02) counteracted the estradiol increase in total C-kinase activity, which was only 45% over control values. We conclude that treatment with a dopamine agonist and estradiol, which have antagonistic effects on the pituitary, exerts an opposite regulation of C-kinase activity.

Protein kinase C activity and expression in normal and adenomatous human pituitaries

“…Lastly, in the 3 tumors obtained from patients treated with the DA agonist or the SRIH analog, PKC activity was much lower than in the other tumors. This result is in agreement with a previous study showing that in vivo treatment with the DA agonist CV 205-502 induces a decrease in pituitary PKC activity both in rats treated with estradiol and in those not treated with estradiol (Birman et al, 1989). This study, which needs to be extended to a larger number of observations, suggests that these molecules exert their in vivo biological effects (inhibition of hormone release, reduction of tumor size) in part by regulating PKC activity.…”

“…The method used was as described by Birman et al (1989). Briefly, particulate and soluble fractions were prepared from a 4To whom correspondence and reprint requests should be addressed.…”

Selective loss of substrate recognition induced by the tumour-associated D294G point mutation in protein kinase Cα

“…Viral supernatant was removed and monolayers of infected cells were recovered by using a stream of PBS [140 mM NaCl\27 mM KCl\8 mM Na # HPO % \1.5 mM KH # PO % (pH 7.4)]. Normal and mutated PKCα were partly purified by the method of Birman et al [19] with a DEAE-cellulose (DE-52) column. Elution conditions were established with a salt gradient ranging from 50 to 200 mM NaCl.…”

Μορφολογικη Μελετη Της Εξελιξης Του Μαστου Θηλεων Ποντικιων C3h/Sy Μετα Απο Προφυλακτικη Χορηγηση Ταμοξιφενης Και Cv 205502: Παρατηρησεις Στο Οπτικο Και Ηλεκτρονικο Μικροσκοπιο

“…Η χορήγηση του φαρμάκου σε ασθενείς με προλακτινώματα, επιφέ ρει μείωση των διαστάσεων του όγκου, κατά την κεντρική του, κυρίως, μοίρα. Τα αντίστοιχα ιστολογικά ευρήματα περιλαμβάνουν μείωση του με γέθους των κυττάρων του όγκου και ελάττωση της εκκριτικής τους δρα στηριότητας, καθώς και αύξηση του αριθμού των κοκκίων, που περιέχουν προλακτίνη (Birman 1989). Σχετικά με το μηχανισμό αυτής της δράσης, βρέθηκε, ότι το CV αναστέλλει την πρωτεϊνοκινάση-C (που διεγείρεται απο τα οιστρογόνα), η οποία σ' αυτό το σύστημα μελέτης φέρεται να συμμετέχει στον κυτταρικό πολλαπλασιασμό και στη σύνθεση της προλακτίνης.…”