Role of gonadotropin-releasing hormone-II and its receptor in swine reproduction

The pig represents the only livestock mammal capable of producing a functional protein for the second mammalian form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II). To examine the role of GnRH-II and its receptor in pig reproduction, we produced a unique swine line with ubiquitous knockdown of endogenous GnRHR-II levels (GnRHR-II knockdown [KD]), which is largely the focus of this review. In mature GnRHR-II KD males, circulating testosterone concentrations were 82% lower than littermate control boars, despite similar luteinizing hormone (LH) levels. In addition, nine other gonadal steroids were reduced in the serum of GnRHR-II KD boars, whereas adrenal steroids (except 11-deoxycortisol) did not differ between lines. Interestingly, testes from GnRHR-II KD males had fewer, hypertrophic Leydig cells and fewer, enlarged seminiferous tubules than control testes. As expected, downstream reproductive traits such as androgen-dependent organ weights and semen characteristics were also significantly reduced in GnRHR-II KD versus control boars. Next, we explored the importance of this novel ligand/receptor complex in female reproduction. Transgenic gilts had fewer, but heavier, corpora lutea with smaller luteal cells than littermate control females. Although the number of antral follicles were similar between lines, the diameter of antral follicles tended to be larger in GnRHR-II KD females. In regard to steroidogenesis, circulating concentrations of progesterone and 17β-estradiol were lower in transgenic compared to control gilts, even though serum levels of follicle-stimulating hormone and LH were similar. Thus, GnRH-II and GnRHR-II represent a potential avenue to enhance fertility and promote the profitability of pork producers.