PMID- 28195074 OWN - NLM STAT- MEDLINE DCOM- 20170608 LR - 20170608 IS - 1899-1505 (Electronic) IS - 0867-5910 (Linking) VI - 67 IP - 6 DP - 2016 Dec TI - Induction of autophagy in the porcine corpus luteum of pregnancy following anti-androgen treatment. PG - 933-942 AB - Experimentally induced androgen deficiency during late pregnancy leads to decreased progesterone synthesis in the porcine corpus luteum (CL), which suggested an onset of functional luteolysis. It was shown that luteal regression in mammals involves not only apoptosis but also autophagy. Therefore, this study aimed to examine whether anti-androgen flutamide treatment during late pregnancy in pigs induces apoptosis and/or autophagy within luteal cells. Flutamide (50 mg/kg b.w.) was administered into pregnant gilts between 83 - 89 (GD90F) or 101 - 107 (GD108F) gestational days (GD). CLs were retrieved on day 90 or 108 of pregnancy (n = 3/each group). Detection of apoptosis was performed by TUNEL assay and assessment of cleaved caspase 3 level. Both assays revealed that luteal rate of apoptosis was unaffected by flutamide treatment either in the GD90F or GD108F groups. Moreover, pro-apoptotic protein Bax was downregulated on GD108. The autophagy was examined by expression of two markers, LC3-II and Lamp1. Flutamide led to greater expression of LC3-II protein form in the GD90F and GD108F groups. Likewise, the mRNA and protein levels of Lamp1 were elevated in both flutamide-treated groups. The activation of autophagy is regulated by Beclin 1 and the increased Beclin 1 mRNA and protein expression was found in the GD90F and GD108F groups. Beclin 1 is a Bcl-2-binding protein, thus Beclin1/Bcl-2 interactions were examined using immunoprecipitation. Beclin 1/Bcl-2 complexes were less abundant following flutamide treatment in both flutamide-exposed groups. In summary, we concluded that androgen deficiency induced autophagy by disrupting Beclin 1/Bcl-2 interplay in the porcine CL during pregnancy. The role of autophagy in luteal regression in pigs requires further evaluation. FAU - Grzesiak, M AU - Grzesiak M AD - Department of Endocrinology, Institute of Zoology, Jagiellonian University, Cracow, Poland. m.grzesiak@ur.krakow.pl. AD - Department of Animal Physiology and Endocrinology, University of Agriculture, Cracow, Poland. FAU - Knapczyk-Stwora, K AU - Knapczyk-Stwora K AD - Department of Endocrinology, Institute of Zoology, Jagiellonian University, Cracow, Poland. FAU - Slomczynska, M AU - Slomczynska M AD - Department of Endocrinology, Institute of Zoology, Jagiellonian University, Cracow, Poland. LA - eng PT - Journal Article PL - Poland TA - J Physiol Pharmacol JT - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JID - 9114501 RN - 0 (Androgen Antagonists) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Beclin-1) RN - 0 (Lysosomal-Associated Membrane Protein 1) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 76W6J0943E (Flutamide) SB - IM MH - Androgen Antagonists/*pharmacology MH - Animals MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Autophagy/*drug effects MH - Beclin-1/metabolism MH - Corpus Luteum/*drug effects/metabolism MH - Female MH - Flutamide/pharmacology MH - Luteal Cells/drug effects/metabolism MH - Lysosomal-Associated Membrane Protein 1/metabolism MH - Microtubule-Associated Proteins/metabolism MH - Pregnancy MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - RNA, Messenger/metabolism MH - Swine EDAT- 2017/02/15 06:00 MHDA- 2017/06/09 06:00 CRDT- 2017/02/15 06:00 PHST- 2016/10/04 00:00 [received] PHST- 2016/12/23 00:00 [accepted] PHST- 2017/02/15 06:00 [entrez] PHST- 2017/02/15 06:00 [pubmed] PHST- 2017/06/09 06:00 [medline] PST - ppublish SO - J Physiol Pharmacol. 2016 Dec;67(6):933-942.