Endocrine Abstracts (2011) 26 OC5.2

Site specific overexpression of urocortin 2 results in modulation of steroidogenesis in vivo

A Spyroglou1, A Hill1, K Mueller-Peltzer1, J Deussing2 & F Beuschlein1

1Endocrine Research Unit, Medical Clinic Innenstadt, LMU, Munich, Germany; 2Max Planck Institute of Psychiatry, Munich, Germany.

Urocortin 2 (Ucn2) is a recently identified neuropeptide of the CRF-Family, involved in homeostatic mechanisms for stress response and control of anxiety. To further elucidate Ucn2 effects on steroidogenesis, we developed a mouse model with Ucn2 overexpression in the adrenals, gonads and parts of the hypothalamus, by crossbreeding SF1-Cre+/− mice with R26stop UCN2/stop UCN2 mice. Following genotypes were obtained: SF1-Cre−/−/ R26+/stop UCN2 (controls) and SF1-Cre+/−/ R26+/stop UCN2 (Ucn2OE). Adrenal glands, ovaries, testes and trunk blood of two-month-old animals were collected. Plasma concentration of corticosterone and Ucn2 were measured with commercially available immunoassays. Expression levels of Ucn2 and steroidogenic genes were quantified by real-time PCR analysis.

A 3.5-fold elevated plasma Ucn2 (P<0.001) and a 20-fold increased Ucn2 expression in adrenals (P<0.001) of male and female Ucn2OE could be documented. A lower expression of StAR (P<0.05), cyp11a1 (P<0.001) and cyp11b1 (P<0.05) could be demonstrated in adrenals of female Ucn2OE, together with reduced plasma corticosterone values (P=0.05). In contrast, 6-fold higher Ucn2 expression in ovaries was associated with significant increase of StAR (P<0.05) and cyp11a1 (P<0.05). On the contrary, steroidogenic enzymes’ expression in male adrenals and plasma corticosterone levels did not differ from controls (StAR P=0.29, cyp11a1 P=0.70, cyp11b1 P=0.99, corticosterone P=0.47). Surprisingly, Ucn2 expression in testes was comparable to controls and no effects on steroidogenesis could be documented.

These data demonstrate that Ucn2 overexpression in the female mouse results in downregulation of steroidogenesis in the adrenal, suggesting a stress coping behaviour and increased steroidogenesis in the ovary, an observation not confirmed in male gonads. The gender specific discrepancies will be further investigated.

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