Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone

Abstract

Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species.

Keywords:

• dog
• gonadotropins
• germ cells
• Leydig cells
• nonhuman primates
• rodent
• Sertoli cells
• testosterone
• testis
• toxicology

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors would like to thank Dr. Dianne Creasy, Huntingdon Life Sciences, East Millstone, USA and Robert E. Chapin, Pfizer Inc., Groton, USA for the opportunity to contribute to this journal issue. The authors are especially grateful to Dr. Dianne Creasy for help with documenting rat and dog spermatogenic lesions, Dr. Tony M. Plant, PhD, University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, USA, for critical comments, to Dr. William H. Walker, PhD, for sharing some of the review material, to Prof. Dr. Zheng-Wei Yang, Morphometric Research Laboratory, North Sichuan Medical College, Sichuan, China and Dr. C Marc Luetjens, Covance Laboratories GmbH, Muenster, Germany, for help with the micrographs and to Dr. Sandra Goericke-Pesch, Department of Large Animal Sciences, Frederiksberg, Denmark for help with documenting the alterations in the dog testis. We also thank Ms. Joyce Peterson, Magee-Womens Research Institute, Pittsburgh, USA, for organizing the bibliography.

Funding

SR was supported by NIH grants U54HD08610 and R01HD72189 (PI, Dr. Tony M. Plant).