We have recently shown that corticotropin-releasing hormone (CRH) is a major thyrotropin (TSH)-releasing factor in amphibians, but we have also found that, besides CRH, other hypothalamic substances stimulate TSH secretion in frog. In order to characterize novel TSH secretagogues, we have investigated the effect of frog (Rana ridibunda) vasoactive intestinal polypeptide (VIP) (fVIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) (fPACAP38 and PACAP27) on TSH release from bullfrog (Rana catesbeiana) pituitary cells in primary culture. Incubation of pituitary cells for 24 h with graded concentrations of fVIP, fPACAP38 and PACAP27 (10-9 to 10-6 M) induced a dose-dependent stimulation of TSH release with minimum effective doses of 10-9 M for fVIP and 10-8 M for fPACAP38 and PACAP27. The PAC1-R/VPAC2-R antagonist PACAP6-38 (10-7 and 10-6 M) dose-dependently suppressed the stimulatory effects of fVIP and fPACAP38 (10-7 M each). Likewise, this antagonist (10-6 and 10-5 M) dose-dependently attenuated the stimulatory effect of PACAP27 (10-7 M). On the other hand, the VPAC1-R/VPAC2-R antagonist [d-pCl-Phe6, Leu17]VIP (10-6 and 10-5 M) dose-dependently inhibited the stimulatory effect of fVIP (10-9 M) and PACAP27 (10-8 M), but did not affect the response to fPACAP38 (10-8 M). These data indicate that, in amphibians, the activity of thyrotrophs can be regulated by VIP and PACAP acting likely through VPAC2-R and PAC1-R.
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