Chronic treatment by the calcium channel blocker +/- PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo.
In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with +/- PN 200-110 (3 mg.kg-1.day-1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 +/- 4.9 vs 95.0 +/- 9.1 micrograms/l, p less than 0.0001) and pituitary weight (19.9 +/- 0.4 vs 23.0 +/- 0.6 mg, p less than 0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.
Touraine
P
P
INSERM U.223, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Birman
P
P
Bai-Grenier
F
F
Dubray
C
C
Peillon
F
F
Joubert
D
D
D000818:Animals; D002121:Calcium Channel Blockers; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D017275:Isradipine; D009929:Organ Size / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology*; D010902:Pituitary Gland / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D004958:Estradiol; D011388:Prolactin; D011493:Protein Kinase C; D017275:Isradipine