Effects of synthetic progestagens on the mRNA expression of androgen receptor, progesterone receptor, oestrogen receptor alpha and beta, insulin-like growth factor-1 (IGF-1) and IGF-1 receptor in heifer tissues.

Synthetic progestagens like melengestrol acetate (MGA) are widely used for oestrus synchronization and for growth promotion in cattle production. The metabolic effects exceed its primary potency as a progestagen. It is speculated that MGA stimulates follicle development and thereby endogenous oestrogen production, but inhibits ovulation. To investigate the dose-dependent effects on mRNA expression levels, six heifers were fed for 8 weeks with different levels of MGA (0.5, 1.5, 5 mg) daily and two heifers served as controls. The expression of steroid receptor mRNA [androgen receptor (AR), progesterone receptor (PR), oestrogen receptor (ER) ERalpha and ERbeta], insulin-like growth factor-1 (IGF-1) and its receptor were quantified in liver, neck (m. splenius) and shoulder muscularity (m. deltoideus). Plasma concentrations of IGF-1 were quantified by radioimmunoassay. In treated animals the MGA plasma levels were elevated over the complete treatment period, corresponding to the MGA treatment concentrations. IGF-1 concentrations of control animals were at constant levels. Plasma levels for oestradiol (E2) and IGF-1 were increased in the low MGA treatment group. Overdosed MGA decreased progesterone (P4) and E2 levels. To quantify the IGF-1 and all receptor mRNA transcripts, sensitive and reliable real-time reverse transcription-polymerase chain reaction (RT-PCR) quantification methods were developed and validated in the LightCycler. A dose-dependent relationship between increasing MGA concentration and mRNA expression was observed in liver for AR and IGF-1 receptor, and in neck muscularity for IGF-1. ERalpha in liver and neck muscle showed a trend of increasing expression.