Submitted on August 18, 2007
Accepted on September 30, 2007
Common and specific effects of the two major forms of prolactin (PRL) in the rat testis
Valencia L Williams1, Ariel DeGuzman1, Hong Dang1, Mitsumori Kawaminami2, Timothy WC Ho1, David G Carter3, and Ameae M. Walker4*
1 Biomedical Sciences, University of California, Riverside, Riverside, California, United States
2 Veterinary Physiology, Kitasato University, Towada,, Aomori, Japan
3 Botany and Plant Sciences, University of California, Riverside, Riverside, California, United States
4 Division of Biomedical Sciences, University of California, Riverside,, California, United States
* To whom correspondence should be addressed. E-mail: ameae.walker{at}ucr.edu.
Prolactin (PRL) has both stimulatory and inhibitory effects on testicular function; a finding we hypothesized may be related in part to the form of the hormone present/administered. Pituitary secretion profiles of early pubescent versus mature males found PRL released from early pubescent pituitaries had about twice the degree of phosphorylation. Treatment of mature males with either unmodified PRL (U-PRL), or phosphorylated PRL (via the molecular mimic - S179D PRL) for a period of 4 weeks (circulating ~50 ng/ml) showed testosterone (T) decreased by ~35% only by treatment with the phospho-mimic, S179D PRL. Given the specificity of this effect, it was surprising that both forms of PRL decreased testicular expression of 3
-hydroxysteroid dehydrogenase (3-HSD) and steroidogenic acute regulatory protein (StAR). Both forms also increased expression of the LH receptor, but only S179D PRL increased the ratio of short to long PRL receptors. Endogenous PRL and LH levels were unchanged in all groups in this time frame, suggesting that effects on gene expression were directly on the testis. TUNEL analysis with staining for 3-HSD and morphometric analysis showed that S179D PRL, but not U-PRL, increased apoptosis of Leydig cells, a finding supported by increased staining for Fas/Fasligand in the testicular interstitium. S179D PRL, but not U-PRL, also increased apoptosis of primary spermatogonia, and U-PRL, but not S179D PRL, decreased apoptosis of elongating spermatids. Thus in mature males, hyperprolactinemic levels of both forms of PRL have common effects on steroidogenic proteins, but specific effects on the apoptosis of Leydig and germ cells.
