Copulsatile release of thyrotropin and prolactin in normal and hypothyroid subjects

In healthy subjects, thyroid-stimulating hormone (TSH) and prolactin (PRL) are secreted in a pulsatile fashion. However, the factors that control the generation of these pulses are unknown. Since thyrotropin-releasing hormone (TRH) and dopamine (DA) affect levels of both hormones, pulsatile TRH or DA input to the pituitary gland may lead to pulsatile secretion of both TSH and PRL. In this case, TSH and PRL should exhibit significant nonrandom pulse concordance rates. To test this hypothesis, we studied 11 healthy subjects (5 women in the early follicular phase and 6 men) and 11 subjects with primary hypothyroidism (5 untreated and 6 euthyroid on 1-thyroxine therapy). To further test the specific hypothesis that pulsatile TRH entrains pulsatile TSH and PRL secretion, we restudied the 6 treated hypothyroid subjects on the final day of a 9-day constant infusion of TRH. In each study, blood samples were drawn every 15 min for 24 h, and TSH and PRL levels were measured by immunoradiometric assays. Hormone pulses were located by Cluster analysis. Nonrandom TSH and PRL pulse coincidence rates were assessed by a statistically based computer algorithm, which compares observed pulse concordance rates to those expected by chance. In the healthy men and women and the treated hypothyroid subjects, TSH and PRL were copulsatile in a significantly nonrandom fashion. Of TSH pulses 36-45% occurred within 15 min of PRL pulses, while 37-67% of PRL pulses occurred within 15 min of TSH pulses. Similar pulse concordance rates were seen in treated hypothyroid subjects receiving constant TRH infusions. Thus, there appears to be a central factor or factors that stimulate the copulsatile release of TSH and PRL. However, TRH does not appear to play a role in this phenomenon, and the underlying pulse generator(s) for both hormones remains to be elucidated.