Aberrant secretion of 10 gonadal steroids in gonadotropin-releasing hormone II receptor knockdown boars

Authors: DESAULNIERS, AMY - University Of Nebraska; CEDERBERG, REBECCA - University Of Nebraska; Lents, Clay; WHITE, BRETT - University Of Nebraska

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/1/2017
Publication Date: 10/19/2017
Citation: Desaulniers, A.T., Cederberg, R.A., Lents, C.A., White, B.R. 2017. Aberrant secretion of 10 gonadal steroids in gonadotropin-releasing hormone II receptor knockdown boars. [Abstract] In: Proceedings 14th Annual Gilbert S. Greenwald Symposium on Reproduction and Regenerative Medicine, Kansas City, KS, Oct. 19-20, 2017. p. 36. Available: http://www.kumc.edu/greenwald-symposium/history.html

Interpretive Summary:

Technical Abstract: Paradoxically, the second mammalian GnRH isoform (GnRH-II) and its receptor (GnRHR-II) are not physiological regulators of gonadotropin secretion. Instead, data from our laboratory suggests that both are abundantly produced in the porcine testis and mediate testosterone secretion independent of luteinizing hormone (LH). To further study the role of GnRH-II and its receptor in pigs, our laboratory generated a GnRHR-II knockdown (KD) swine line with 70% lower levels of testicular GnRHR-II mRNA compared to littermate control boars. During pubertal development, testosterone concentrations tended to be reduced in transgenic versus littermate control boars, yet LH concentrations were unaffected. The objective of this study was to compare the secretory patterns of testosterone and circulating concentrations of 16 other steroids in adult GnRHR-II KD (n = 5) and littermate control (n = 5) males. Boars were fit with indwelling jugular cannulae and blood was collected every 15 min for 8 h. Serum was assayed for testosterone concentration via radioimmunoassay. Samples (1/animal) were also subjected to high performance liquid chromatography tandem mass spectrometry at Biocrates Life Sciences AG (Innsbruck, Austria). Transgenic boars tended to produce fewer pulses of testosterone than littermate controls (P < 0.10). Amplitude of pulses was reduced in transgenics (P < 0.05) but pulse duration was unaffected (P > 0.10). GnRHR-II KD boars also tended to have lower minimum, maximum and mean concentrations of testosterone (P < 0.10). Likewise, area under the curve tended to be reduced in transgenics (P < 0.10). Mass spectrometry revealed that production of corticosteroids was largely unaffected in GnRHR-II KD boars; however, gonadal steroids were dramatically impacted. Serum concentrations of progestogens (17a-hydroxyprogesterone and progesterone), androgens (dehydroepiandrosterone, dihydrotestosterone and androsterone) and estrogens (estrone and 17ß-estradiol) were reduced (P < 0.05) in transgenic compared to littermate control boars. In addition, concentrations of testosterone, dehydroepiandrosterone sulfate and androstenedione tended to be lower in GnRHR-II KD boars (P = 0.10). Ultimately, these data demonstrate that GnRH-II and its receptor are critical modulators of steroidogenesis within porcine Leydig cells. Partially supported by USDA NIFA AFRI ELI predoctoral fellowship (2017-67011-26036; ATD) and AFRI (2017-67015-26508; BRW) funds.