Acute and chronic changes in adenohypophyseal hormone secretion in sheep during zeranol administration

The effect of zeranol on circulating plasma concentrations of 5 adenohypophyseal (anterior pituitary gland) hormones was investigated in growing, castrated male sheep in 3 studies: after IM injection of 1 mg of zeranol (acute study), during a 6-week period after subcutaneous implantation of 12 mg of zeranol (chronic study), and during a 4-hour continuous IV infusion of gonadotropin-releasing hormone (Gn-RH) plus thyrotropin releasing hormone (TRH), 10 micrograms/hour. The sheep used in the chronic study (challenge study) were the same animals used in the 6-week implant study. Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), thyroid-stimulating hormone (TSH), and growth hormone (GH) were measured by specific radioimmunoassay. Injection of zeranol resulted in a transient decrease in circulating LH and prolonged reduction in FSH concentrations during the 24-hour sampling period. Plasma concentrations of PRL, TSH, and GH in zeranol-injected and control animals were not different. Implantation of zeranol caused chronic reduction in plasma LH and FSH, an increase in PRL, and no change in plasma GH or TSH concentrations compared with values for control animals. In the challenge study, IV infusion of Gn-RH and TRH caused a significant increase in the concentration of each of the 5 hormones compared with preinfusion values, regardless of zeranol treatment. When the hormone-response profiles were compared between zeranol-treated and control sheep in this challenge study, only the LH response was different--being greater in zeranol-treated sheep. Generally, the administration of zeranol resulted in a more pronounced alteration in basal and stimulated secretion of reproductive hormones such as LH, FSH, and PRL than in GH or TSH, which are more commonly associated with growth and development.