The role of thyroid hormone in testicular development and function

Abstract

Thyroid hormone is a critical regulator of growth, development, and metabolism in virtually all tissues, and altered thyroid status affects many organs and systems. Although for many years testis has been regarded as a thyroid hormone unresponsive organ, it is now evident that thyroid hormone plays an important role in testicular development and function. A considerable amount of data show that thyroid hormone influences steroidogenesis as well as spermatogenesis. The involvement of tri-iodothyronine (T(3)) in the control of Sertoli cell proliferation and functional maturation is widely accepted, as well as its role in postnatal Leydig cell differentiation and steroidogenesis. The presence of thyroid hormone receptors in testicular cells throughout development and in adulthood implies that T(3) may act directly on these cells to bring about its effects. Several recent studies have employed different methodologies and techniques in an attempt to understand the mechanisms underlying thyroid hormone effects on testicular cells. The current review aims at presenting an updated picture of the recent advances made regarding the role of thyroid hormones in male gonadal function.

Figure 1

Schematic diagram illustrating the morphological structure of adult Sertoli cells and their interactions with the different germ cells within the seminiferous epithelium. The relative locations of tight junctions between adjacent Sertoli cells, which create the blood-testis barrier (BTB) and divide the seminiferous tubule into basal and adluminal compartments, are indicated.

Figure 2

In situ hybridization autoradiograms of type 2 iodothyronine deiodinase (D2) expression in rat seminiferous epithelium. Dark (A) and bright (B) field microscopy show longitudinal sections of the seminiferous epithelium with intense labeling for D2 mRNA in spermatids. Tubule 1 is on stage III/IV of the cycle, in which spermatids are in the process of elongation and localized more internally in the tube wall. Tubule 2 is on stage VII/VIII of the cycle. (C) Higher magnification of part of tubule 2 showing interstitial cells (IC) negative for D2 mRNA and intense D2 labeling in elongated spermatids close to the lumen. A negligible background can de observed. In D, a high magnification of a cross-section of seminiferous tubule in stage V of the cycle shows D2-positive spermatids localized in the middle of the tubule. Note that spermatogonia (SG) are negative. Scale bars, 50 µm (A, B); 12 µm (C, D).

Figure 3

The control (+/?) and rdw rat testes stained with HE. (a) 2-week-old control (+/?) rat testis. Some spermatocytes can be seen in the center of the seminiferous tubules (arrows) (magnification: x140). (b) 4-week-old control (+/?) rat testis. Spermatocytes (arrows) become large but initial meiotic division has not yet been detected (magnification: x140). (c) 8-week-old control (+/?) rat testis. Seminiferous tubules fully developed (magnification: x140). (d) Enlarged picture of (c). Even at high magnification (x560), no difference from the normal adult germinal epithelium can be detected. (e) 4-week-old rdw rat testis. Some spermatocytes (arrows) can be seen in the seminiferous tubules. This corresponds to the 2-week-old normal one (magnification: x140). (f) 8-week-old rdw rat testis. Spermatocytes (arrows) become large but initial meiotic division has not yet been detected. This corresponds to the 4-week-old normal one (magnification: x140). (g) 22-week-old rdw rat testis. Seminiferous tubules apparently seem to be fully developed. This corresponds to the 8-week-old normal one (magnification: x140). (h) Enlarged picture of Figure g (magnification: x560). (Permission taken from the publisher, Develop. Growth Differ. (2004) 46, 327–334).