The effects of substance P (SP), angiotensin II, oxotremorine and prostaglandin D2 (PG D2) on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Either SP (100 micrograms/kg), angiotensin II (500 micrograms/kg), oxotremorine (1.0 mg/kg) or PGD2 (500 micrograms/kg) was injected intravenously or intraperitoneally, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by means of a specific radioimmunoassay for each. The hypothalamic immunoreactive TRH (ir-TRH) contents were significantly increased by oxotremorine or SP and significantly decreased by angiotensin II, but no by PG D2. The plasma ir-TRH concentrations were significantly increased by angiotensin II, but not by oxotremorine, SP or PG D2. The plasma TSH levels were significantly increased by angiotensin II and significantly decreased by oxotremorine, SP or PG D2 in a dose-related manner. The plasma ir-TRH and TSH responses to cold were inhibited by oxotremorine, SP or PG D2, but enhanced by angiotensin II. The plasma TSH response to TRH was inhibited by SP, but enhanced by angiotensin II. The plasma TSH response to TRH did not differ from that of the control after PG D2 injection. In the haloperidol- or para-chlorophenylalanine (PCPA)-pretreated group, the inhibitory effect of PG D2 or oxotremorine on TSH release was prevented, while in the L-DOPA- or 5-hydroxytryptophan (5-HTP)-pretreated group, the inhibitory effect of SP on TSH release was prevented.(ABSTRACT TRUNCATED AT 250 WORDS)