Interaction between substance P and TRH in the control of prolactin release

Substance P (SP) may participate as a paracrine and/or autocrine factor ill the regulation of anterior pituitary function. This project studied the ef fect of TRH on SP content and release from anterior pituitary and the role of SP in TRH-induced prolactin release. TRH (10(-7) M), but not vasoactive intestinal polypeptide (VIP), increased immunoreactive-SP (ir-SP) content a nd release from male rat anterior pituitary in vitro. An anti-prolactin ser um also increased ir-SP release and content. In order to determine whether intrapituitary SP participates in TRH-induced prolactin release, anterior p ituitaries were incubated with TRW (10(-7) M) and either WIN 62,577, a spec ific antagonist of the NK1 receptor, or a specific anti-SP serum. Both WIN 62,577 (10(-8) and 10(-7) M) and the anti-SP serum (1:250) blocked TRH-indu ced prolactin release. In order to study the interaction between TRH and SP on prolactin release, anterior pituitaries were incubated with either TRH (10(-7) M) or SP, or with both peptides. SP (10(-7) and 10(-6) M) by itself stimulated prolactin release. While 10(-7) M SP did not modify the TRH eff ect, 10(-6) M SP reduced TRH-stimulated prolactin release. SP (10(-5) M) al one failed to stimulate prolactin release and markedly decreased TRH-induce d prolactin release. The present study shows that TRH stimulates ir-SP rele ase and increases ir-SP content in the anterior pituitary. Our data also su ggest that SP may act as a modulator of TRH effect on prolactin secretion b y a paracrine mechanism.