Dephosphorylation/inactivation of tyrosine hydroxylase at the median eminence of the hypothalamus is required for suckling-induced prolactin and adrenocorticotrop hormone responses

Abstract

We have recently found that dopamine (DA) released from terminals of the hypothalamic neuroendocrine dopamine (NEDA) neurons plays a role not only in prolactin (PRL), but also in adrenocorticotrop hormone (ACTH) secretion, without having any influence on α-melanocyte-stimulating hormone (α-MSH) release in lactating dams. The aim of our present studies was to further investigate this DAerg regulation of ACTH using consecutively applied physiological stimulation (suckling) and pharmacological inhibition of the rate-limiting enzyme of DA synthesis (tyrosine hydroxylase, TH) by α-methyl-p-tyrosine (α-MpT) that acutely affect secretion of these pituitary hormones during lactation. Following 4 h separation period, two experimental groups were formed. In the first group, lactating rats were assembled with their litters for 60 min prior to α-MpT. In the second group, the α-MpT was injected first and 60 min later suckling stimulus was applied. Plasma samples were taken in every 15 min during the 90 min experimental period. Concentrations of plasma PRL, ACTH and α-MSH were measured by specific RIAs. Both stimuli applied in the first sequence, significantly elevated plasma PRL and ACTH levels in separated lactating dams, without having any effect on α-MSH secretion. Suckling applied in the first sequence was able to block the α-MpT-induced elevation of ACTH secretion, while PRL response was also significantly attenuated. α-MpT pretreatment prevented both PRL and ACTH responses to suckling stimulus. Investigating the dephosphorylation/inactivation of TH in the arcuate nucleus-ME (TIDA) regions, no pTH-immunoreactive perikarya or terminals can be found in continuously suckled dams. In contrast, after 4 h separation of the mothers from their litters, pTH-immunoreactivity can be clearly visualized in the external zone of ME. In α-MpT pretreated mothers following 4 h separation no pTH positive terminals are visible. No changes in the TH immunostaining can be observed in any of these experimental groups. In conclusion, dephosphorylation/inactivation of TH (the rate-limiting enzyme of the DA biosynthesis) in NEDA neurons is required for suckling-induced PRL and ACTH responses.