Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulum Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

• Published in: Journal of endocrinology Vol. 195; no. 1; pp. 17 - 27
• Main Authors: Anhê, Gabriel F, Nogueira, Tatiane C A, Nicoletti-Carvalho, José E, Lellis-Santos, Camilo, Barbosa, Helena C, Cipolla-Neto, José, Bosqueiro, José R, Boschero, Antonio C, Bordin, Silvana
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.10.2007; Portland Press
• Subjects: Adaptation, Physiological; Animals; Biological and medical sciences; Blotting, Western; Cell Line; Cells, Cultured; Dexamethasone - pharmacology; Endocrine pancreas; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Glucocorticoids - metabolism; Hormones. Régulation; Insulin - analysis; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - chemistry; Islets of Langerhans - metabolism; Lactation - physiology; Oligonucleotides, Antisense - genetics; Phosphorylation; Pregnancy; Prolactin - genetics; Prolactin - metabolism; Rats; Regular papers; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sarcoplasmic Reticulum Calcium-Transporting ATPases - analysis; Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Signal Transduction - drug effects; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transfection - methods; Vertebrates: endocrinology; Pancreatic hormone; Rat; Secretion; Rodentia; Langerhans islet; Gene expression; Glucocorticoid; Insulin; Vertebrata; Mammalia; Adenohypophyseal hormone; Prolactin; Adult animal; Endocrine pancreas; Adaptation
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/JOE-07-0010

During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PRL) action, functional changes that are characterized by increased glucose-induced insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to non-pregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (L3). The expression of the sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in β-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of P19 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.