Effects of TNF-α on penile structure alteration in rats with hyperprolactinemia.

Zhong-Lin Wang,Hong-Huan Chen,Yi-Ting Tsai,William J Huang,Hsiao-Hsin Lin,Ling-Yu Yang,Miklos S Kellermayer

doi:10.1371/journal.pone.0181952

Abstract

This study aimed to investigate the effects of anti-tumor necrosis factor (TNF)-α antibody (Ab) on alteration of penile structure in the hyperprolactinemia (hyperPRL) rat model. HyperPRL was induced in 8-week-old male Sprague-Dawley rats by allografting anterior pituitary (AP) glands under the renal capsule (+AP rats). Rats implanted with cerebral cortex (CX) were used as sham control (+CX rats). At 6 weeks post implantation, rats received either a single intra-testicular dose of TNF-α Ab (12.5 μg/kg) or testosterone replacement (2 doses of testosterone enanthate [TE], 3 mg/kg), and they were sacrificed 1 week later. Blood and penile tissue was collected for analysis. Compared to +CX rats, the +AP group had lower serum testosterone concentration and neuronal nitric oxide synthase (nNOS) expression, but exhibited a higher ratio of collagen III/I in the corpus cavernosum. Smooth muscle content exhibited no significant changes. At 1 week post TNF-α Ab injection, the collagen III/I ratio in the +AP group was decreased, and the smooth muscle content and nNOS expression increased significantly. These findings were comparable to those observed in +AP rats receiving TE. Testicular TNF-α suppresses testosterone release, which in turn results in the erectile dysfunction (ED) seen in hyperPRL. Intra-testicular TNF-α Ab treatment is as effective as testosterone supplementation on penile structure normalization in the hyperPRL model.

Highlights

Prolactin (PRL), a 23 kDa peptide, is secreted from the lactotrophs of the anterior pituitary (AP) gland under the inhibitory control of hypothalamic dopamine
One week after tumor necrosis factor (TNF)-α Ab or TE injection, the collagen III/I ratio in +AP rats was significantly decreased compared to that in the untreated +AP group
Compared to that in the untreated +CX group, collagen III in the +CX group receiving TE was significantly decreased. These findings suggested that intra-testicular TNF-α Ab injection and intra-muscular TE injection has similar effects on penile tissue

Summary

Introduction

Prolactin (PRL), a 23 kDa peptide, is secreted from the lactotrophs of the anterior pituitary (AP) gland under the inhibitory control of hypothalamic dopamine. The main functions of PRL in females are inducing and maintaining lactation during the peripartum and postpartum phases. The role of PRL is less significant. A PRL deficiency in childhood might interfere with development of the reproductive system [1, 2]. Overproduction and subsequently increased blood PRL level, known as hyperprolactinemia (hyperPRL), may be seen.

Objectives

Methods

Results

Discussion

Conclusion