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Neuroendocrine and Reproductive Functions in Male Mice with Targeted Disruption of the Prolactin Gene¹

Department of Physiology, Southern Illinois University School of Medicine (R.W.S., V.C., A.B.), Carbondale, Illinois 62901-6512; and the Department of Physiology and Biology, University of Cincinnati (N.H., W.Z.), Cincinnati, Ohio 45267-0576

Address all correspondence and requests for reprints to: Dr. R. W. Steger, Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901-1625. E-mail: rsteger{at}som.siu.edu

Mice with a targeted disruption (knock-out) of the PRL gene (PRL-KO) were used to study the physiological role of PRL in the control of male neuroendocrine functions related to reproduction. Compared with normal males, PRL-KO mice had significant reductions in median eminence dopamine content, plasma LH levels, LH and FSH secretion in vitro (per mg pituitary), and weights of seminal vesicles and ventral prostate. PRL was not detectable in incubation medium with pituitaries from PRL-KO mice. No alterations were detected in PRL-KO mice in median eminence norepinephrine, plasma testosterone levels, or testosterone release (per mg testis) in vitro with or without LH. No differences were detected in PRL-KO vs. normal male mice in the interval from housing with normal female mice until conception, rate of pregnancy, or the number of live pups per litter. Pituitary weight in PRL-KO mice was increased (1.78 ± 0.22 vs. 3.35 ± 0.20 mg; P < 0.001), presumably due to reduced feedback inhibition and hypertrophy and/or hyperplasia of nonfunctional lactotrophs. These results indicate that the absence of PRL reduces pituitary LH release, attenuates median eminence dopaminergic activity, and affects the growth of seminal vesicles and ventral prostate. Although it was previously shown that PRL can repair the reproductive defect in male pituitary dwarf mice, our current results imply that the PRL deficiency alone is not sufficient to cause male infertility, although there are obvious alterations in reproductive neuroendocrine function in PRL-KO males.

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