Down-regulation of β-adrenergic receptors and up-regulation of estrogen and progesterone receptors induced in the reproductive system of female veal calves by dietary clenbuterol

Giovanni Re From the Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, via Nizza 52, I-10126 Turin, Italy.

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Paola Badino From the Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, via Nizza 52, I-10126 Turin, Italy.

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Antonella Novelli From the Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, via Nizza 52, I-10126 Turin, Italy.

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Carlo Girardi From the Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, via Nizza 52, I-10126 Turin, Italy.

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SUMMARY

Effects induced by long-term administration of clenbuterol at anabolic dosages (20 µg/kg of body weight for 40 days) on β-adrenergic receptor (β-ar) subtypes, estrogen receptors (er), and progesterone receptors (PgR) in the reproductive system of female veal calves were investigated. Clenbuterol treatment induced a significant (P < 0.01) down-regulation of β-ar subtypes (β1-ar, β2-ar, myometrial high-affinity β2-ar, and ovarian low-affinity β2-ar). On the other hand, a significant (P < 0.01) increase of uterine and ovarian er and PgR receptors was observed in treated calves. Treatment did not affect dissociation constant values of β-ar, er, or PgR. In similar manner, clenbuterol did not significantly modify distribution of er and PgR in the various tissues of the genital tract. In fact, these receptors were significantly (P < 0.05) more concentrated in the uterus than in the vagina in treated and untreated calves. Data indicated that prolonged clenbuterol exposure induced homologous β-ar down-regulation (down-regulation of its specific receptors) and heterologous er and PgR up-regulation (up-regulation of different types of receptors, not specifically bound by clenbuterol) in the genital tract of veal calves. Modification of the receptorial status could be reasonably related to the pathologic changes observed in long-term treated calves (eg, hydrometra, dilatation of uterine glands, cystic ovaries). The increased concentrations of er and PgR suggested the possible existence of subcellular mechanisms regulated by repeated β-adrenergic stimulation.

SUMMARY

Effects induced by long-term administration of clenbuterol at anabolic dosages (20 µg/kg of body weight for 40 days) on β-adrenergic receptor (β-ar) subtypes, estrogen receptors (er), and progesterone receptors (PgR) in the reproductive system of female veal calves were investigated. Clenbuterol treatment induced a significant (P < 0.01) down-regulation of β-ar subtypes (β1-ar, β2-ar, myometrial high-affinity β2-ar, and ovarian low-affinity β2-ar). On the other hand, a significant (P < 0.01) increase of uterine and ovarian er and PgR receptors was observed in treated calves. Treatment did not affect dissociation constant values of β-ar, er, or PgR. In similar manner, clenbuterol did not significantly modify distribution of er and PgR in the various tissues of the genital tract. In fact, these receptors were significantly (P < 0.05) more concentrated in the uterus than in the vagina in treated and untreated calves. Data indicated that prolonged clenbuterol exposure induced homologous β-ar down-regulation (down-regulation of its specific receptors) and heterologous er and PgR up-regulation (up-regulation of different types of receptors, not specifically bound by clenbuterol) in the genital tract of veal calves. Modification of the receptorial status could be reasonably related to the pathologic changes observed in long-term treated calves (eg, hydrometra, dilatation of uterine glands, cystic ovaries). The increased concentrations of er and PgR suggested the possible existence of subcellular mechanisms regulated by repeated β-adrenergic stimulation.

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