Sulfamethazine advances puberty in male chicks by effecting a rapid increase in gonadotropins

A sulfonamide, sulfamethazine (SMZ) has been shown to have a robust, progonadal effect. The mechanism of action of SMZ, however, is unknown. Our hypothesis is that the compound may act centrally and/or at the level of the pituitary. Four experiments were completed to test that hypothesis. Chicks exposed to a continuous photoperiod and fed a diet containing 0.2% SMZ showed an exponential increase in testes size. When 6 weeks of age (5 weeks on the SMZ diet), experimentals had testes weight nine times heavier than controls. Profiles for thyroid and gonadotropin plasma hormones suggested that T(3) was transiently lower in experimentals solely during the first week on treatment, while thyroxine levels were not different from controls. In contrast, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly elevated at the initial 1-week sampling point and remained elevated throughout the entire experiment. In a follow-up study, LH was found significantly higher than controls by 48 h after initially consuming the compound. When T(3) was added to the SMZ diet at 0.5 ppm, the progonadal effect of SMZ was attenuated. Importantly, chronic intake of T(3) delayed but did not block the stimulatory effect of SMZ for increasing plasma LH. We conclude that since one of the primary effects of SMZ is to increase rapidly plasma gonadotropins, data suggest the compound is acting at the level of the brain or pituitary to stimulate early gonadal development in chicks.