Endocrine Abstracts (2013) 32 P601 | DOI: 10.1530/endoabs.32.P601

Flutamide-induced alterations in CYP17A1 gene expression and local testosterone synthesis in porcine luteal tissue - a new insight into androgens action during pregnancy

Malgorzata Grzesiak1, Katarzyna Knapczyk-Stwora1, Iwona Wieciech1, Renata E Ciereszko2 & Maria Slomczynska1

1Department of Endocrinology, Institute of Zoology, Jagiellonian University, Krakow, Poland; 2Department of Animal Physiology, University of Warmia and Mazury, Olsztyn, Poland.

It was established that androgens are able to modulate luteal function during pregnancy by stimulation of corpus luteum (CL) progesterone release. In pigs, CL is the main source of progesterone through the entire gestation. Our previous study revealed that porcine CL is capable of androgen synthesis during second half of pregnancy. Therefore, we suggest that androgens, in addition to progesterone, are essential for the maintenance of pregnancy in pigs.

The aim of the study was to determine whether experimentally restricted access of androgens by antiandrogen flutamide during mid- and late pregnancy influences the androgens action in porcine CL. The specific aims are i) analysis of cytochrome P450 17α-hydroxylase/c17–20 lyase (CYP17A1) mRNA expression (real-time PCR), ii) CYP17A1 protein localization (immunohistochemistry), iii) analysis of testosterone (T) production (radioimmunoassay).

Pregnant gilts were allotted into three experimental (flutamide-treated) and respective control groups. Flutamide was administered subcutaneously (50 mg/kg bw) between days 43–49, 83–89 or days 101–107 of gestation. CLs were obtained on day 50 (GD50), 90 (GD90) or 108 (GD108) of gestation, from ovaries of both flutamide-exposed and control pigs.

Overall, the administration of flutamide led to an increased T concentration in CLs obtained on GD50 and GD108, but a decreased T content in CLs on GD90. These results followed by changes in CYP17A1 mRNA expression, which was upregulated by flutamide on GD50 and GD108, but downregulated in luteal tissue on GD90. CYP17A1 was immunolocalized only in small luteal cells obtained on GD50, GD90 and GD108 from both flutamide-exposed and control animals. However, after flutamide administration, the intensity of immunostaining was higher in CLs on GD50 and GD108, but lower in CLs obtained on GD90.

In conclusion, androgen deficiency during pregnancy in pigs affects luteal T synthesis due to changes in CYP17A1 gene expression depending on the day of pregnancy.

Founded by NSC (2011/03/D/NZ4/00303).

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