Are fasting-induced effects on thyrotropin and prolactin secretion mediated by dopamine?
To investigate whether total caloric deprivation influences TSH and/or PRL responsiveness, seven healthy volunteers fasted overnight (8 h) and were injected iv with a small dose (25 micrograms) of TRH and 30 min later with 40 mg cimetidine (CIM). This combined TRH-CIM test was repeated in the same individuals after a fasting period of 56 h. The TRH-stimulated mean maximal TSH increment fell from 5.1 +/- 1.2 to 1.2 +/- 0.6 microU/ml (P less than 0.01) during fasting. In contrast, both the TRH- and CIM-induced PRL responses were unaffected. To exclude methodologic errors on this reduced TSH responsiveness, an additional four normal subjects fasted for 56 h and then were given TRH alone. Two days later the TRH test was repeated after a fasting period of only 8 h. This experimental design also resulted in a significantly lower TSH response after the longer fasting period than after the shorter period, thus demonstrating that prolonged fasting inhibits TSH responsiveness regardless of whether the starvation period precedes or follows the TRH injection, and regardless of whether the pituitary thyrotrophs are stimulated with TRH plus CIM, or with TRH alone. In an additional seven healthy subjects injected with TRH plus CIM before and after a fasting period of 56 h, a dopamine D-2 receptor blocking agent, metoclopramide (MET), was given orally 90 min before the second TRH-CIM load. This priming with MET failed to restore normal TSH responsiveness in the fasting subjects, thus indicating that the suppressed TSH secretion could not have been mediated through dopamine D-2 receptors. However, since oral pretreatment with MET completely abolished the CIM-elicited PRL response in the fasting subjects, it is reasonable to assume that CIM stimulates PRL release via a reduced dopaminergic inhibition of the pituitary lactotrophs.
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone; D002927:Cimetidine; D011388:Prolactin; D013972:Thyrotropin; D008787:Metoclopramide; D004298:Dopamine