Progesterone decreases tyrosine hydroxylase phosphorylation state and increases protein phosphatase 2A activity in the stalk-median eminence on proestrous afternoon

Abstract

The progesterone (P4) rise on proestrous afternoon is associated with dephosphorylation of tyrosine hydroxylase (TH) and reduced TH activity in the stalk-median eminence (SME), which contributes to the proestrous prolactin surge in rats. In the present study, we investigated the time course for P4 effect on TH activity and phosphorylation state, as well as cAMP levels and protein phosphatase 2A (PP2A) activity and quantity, in the SME on proestrous morning and afternoon. P4 (7.5 mg/kg, s.c.) treatment on proestrous afternoon decreased TH activity and TH phosphorylation state at Ser-31 and Ser-40 within 1 h, whereas morning administration of P4 had no 1 h effect on TH. PP2A activity in the SME was enhanced after P4 treatment for 1 h on proestrous afternoon without a change in PP2A catalytic subunit quantity, whereas P4 treatment had no effect on PP2A activity or quantity on proestrous morning. cAMP levels in the SME were unchanged with 1 h P4 treatment. At 5 h after P4 treatment, TH activity and phosphorylation state declined coincident with an increase in plasma prolactin in both P4-treated morning and afternoon groups. PP2A activity in the SME was unchanged in 5 h P4-treated rat. Our data suggest that P4 action on tuberoinfundibular dopaminergic (TIDA) neurons involves at least two components. A more rapid (1 h) P4 effect engaged only on proestrous afternoon likely involves the activation of PP2A. The longer P4 action on TIDA neurons is evident on both the morning and afternoon of proestrus and may involve a common, as yet unidentified, mechanism.