Biochemical Indices of Tuberoinfundibular Dopaminergic Neuronal Activity during Lactation:A Lack of Response to Prolactin

Abstract

Serum concentrations of prolactin and biochemical estimates of impulse traffic in dopaminergic neurons (neuronal ‘activity’) were compared in rats on the second day of diestrus and in 12-day postpartum lactating rats that were either suckled or were nonsuckled (pup-deprived). Indices of the activities of tuberoinfundibular, tuberohypophyseal and nigrostriatal dopamine (DA) neurons were obtained by measuring the α-methyltyrosine-induced decline of DA concentrations, and the accumulation of dihydroxyphenylalanine (dopa) after the administration of an inhibitor of aromatic L-amino-acid decarboxylase in the median eminence, posterior pituitary and striatum, respectively. Biochemical indices of tuberoinfundibular DA neuronal activity and the content of DA in the anterior pituitary gland were lower in pup-deprived lactating rats than in diestrous controls, and were further reduced by suckling. These changes appeared to be specific for tuberoinfundibular DA neurons since biochemical estimates of tuberohypophyseal and nigrostriatal DA neuronal activity were the same in all three groups of animals. Following pup removal serum prolactin concentrations in the dam decreased to basal levels within 4 h and remained low for at least 72 h. The rate of dopa accumulation in the median eminence of lactating rats increased 4 h after pup removal, but remained significantly lower than diestrous values for 72 h. These results indicate that an acute suckling stimulus activates a neuronal circuit which causes a prompt decrease in tuberoinfundibular DA neuronal activity. This decrease may play a role in the suckling-induced increase in prolactin secretion. Independent of these acute changes, the ‘basal’ activity of tuberoinfundibular DA neurons is reduced in lactating rats. This decrease appears to result from the lack of responsiveness of these neurons to the stimulating actions of prolactin. This is supported by the fact that the rate of dopa accumulation in the median eminence was increased in diestrous animals 12 h after the intracerebroventricular injection of prolactin or 16 h after the administration of haloperidol (which increases serum prolactin concentrations) but these treatments were without effect in lactating animals. The decreased responsiveness of tuberoinfundibular DA neurons in lactating rats to prolactin may contribute to the ability of the anterior pituitary gland in these animals to maintain a high secretion rate of this hormone.

Quantitation of prolactin receptor mRNA in the maternal rat brain during pregnancy and lactation

“…This feedback system becomes insensitive to prolactin and placental lactogen during late pregnancy, however, allowing a large prolactin surge to occur during the night preceding parturition (Grattan & Averill 1995, Fliestra & Voogt 1997. The suppression of negative feedback continues into lactation (Demarest et al 1983, Arbogast & Voogt 1996, an important adaptation allowing a prolonged state of hyperprolactinaemia. We have shown that prolactin stimulation of TIDA neurones involves the transcription factor STAT5b , Lerant et al 2001 and it is known that activation of gene transcription requires the long-form PRL-R (Lesueur et al 1991).…”

Antagonist of Pituitary Adenylate Cyclase Activating Polypeptide Suppresses Prolactin Secretion without Changing the Activity of Dopamine Neurons in Lactating Rats

“…These results indicate that pretreatment with PACAP 6–38 inhibits the early phase of PRL secretion response to suckling without changing the activity of dopaminergic neurons in lactating rats. Several reports also have suggested that the dopamine concentrations in portal blood rise after prolonged pup separation [30], and that suckling decreases the dopamine concentrations [31, 32]and TH activity in ME [33, 34]. Both intravenous and intracerebroventricular administrations of PACAP have been reported to increase TH activity.…”

Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague–Dawley) female rats

“…A related hypoprolactinemic strain with lactation failure, IPL Nu (Cohen et al 1983, 1986a, 1986b, 1988, Jordan et al 1987 shows an altered dopaminergic system, which may be responsible for the hypoprolactinemia, since dopamine, originating in the tuberoinfundibular dopaminergic (TIDA) and periventricular hypophyseal dopaminergic (PHDA) neurons of the arcuate and periventricular hypothalamic nuclei (PeN), is the principal negative regulator of Prolactin (PRL) release (Cohen et al 1985). It has been proposed that the diminished TIDA dopaminergic tone and TH expression and activity observed at the end of pregnancy and during lactation (Demarest et al 1983, Grattan & Averill 1990, Hoffman et al 1994, Arbogast & Voogt 1996, Fliestra & Voogt 1997, Li et al 1999, Andrews et al 2001 are the results of decreased sensitivity to PRL negative feedback and the adaptive response of the hypothalamus to allow for the sustained hyperprolactinemia induced by suckling (Andrews 2005). Alterations in the regulation of the hypothalamic dopaminergic system during the period preceding the initiation of lactation could well underlie the posterior lactation failure of these strains of rats.…”