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Progesterone Advances the Diurnal Rhythm of Tuberoinfundibular Dopaminergic Neuronal Activity and the Prolactin Surge in Ovariectomized, Estrogen-Primed Rats and in Intact Proestrous Rats¹

Department of Physiology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan

Address all correspondence and requests for reprints to: Jenn-Tser Pan, Ph.D., Mental Health Research Institute, The University of Michigan, 205 Zina Pitcher Place, Ann Arbor, Michigan 48109-0720.

A diurnal change of tuberoinfundibular dopaminergic (TIDA) neuronal activity exists in female rats, which is prerequisite for the estrogen-induced afternoon PRL surge. Because progesterone (P₄) administered in the morning can advance and amplify the PRL surge, it is of interest to learn whether its action involves the TIDA neuron. In adult ovariectomized and estrogen-primed Sprague-Dawley rats, P₄ (2 mg/kg, sc), given at 0800 h, exhibited a significant effect in advancing and amplifying the afternoon PRL surge, as determined by both chronic catheterization and decapitation methods of blood sampling. The afternoon decrease of TIDA neuronal activity, as determined by 3,4-dihydroxyphenylacetic acid concentration in the median eminence, was also advanced from 1400 to 1300 h. These effects of P₄ on PRL surge and TIDA neuronal activity were shown to be dose- (from 0.5–4 mg/kg) and estrogen-dependent. To determine whether the effect of P₄ was indeed acting via specific P₄ receptor (PR), we used a PR antagonist, RU486, an antisense oligodeoxynucleotide (ODN) for PR messenger RNA (mRNA), and an antibody against PR in this study, to answer this question. Treatments of RU486 (5 mg x 3, sc) for 1–2 days before, and on the sampling day, were effective in antagonizing the effects of P₄ on TIDA neuronal activity and on PRL secretion. Intracerebroventricular injection of an antisense ODN (4 nM) for PR mRNA or of an antibody (1:1 and 1:5) against PR for 2 days (24 and 48 h before decapitation) also were effective. Treatments of RU486 on the sampling day only, of sense ODN for PR mRNA, or of diluted PR antibody (1:10) were without significant effect. The involvement of P₄ or PR on modulating the TIDA neuronal rhythm and the PRL surge also was shown in proestrous rats. In conclusion, P₄ may play a significant modulatory role on rhythmic changes of the TIDA neuronal activity and the PRL surge in the female rats.

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