Studies on the Regulation of Expression of Luteinizing Hormone Receptor in the Ovary and the Mechanism of Follicular Cyst Formation in Ruminants

Abstract

Abstract. In the series of studies, changes of expression and regulation of luteinizing hormone (LH) receptor in the ovary of domestic ruminants were examined. Furthermore, mechanisms of formation of follicular cysts in domestic ruminants, caused by stress and so on, were endocrinologically elucidated. Results of the studies provide the following conclusions. (1) The quantity of LH receptor in the bovine antral follicles increases rapidly in the latter stage of its development. (2) The quantity of LH receptor and its mRNA in the bovine and caprine corpus luteum increase during their developments. The increase of the receptor in the caprine luteal development is regulated by LH through the receptor mRNA level. (3) At least, three splice variants of LH receptor mRNA exist in the bovine luteal tissue and the variant receptors are expressed at different cellular sites according to its structure. (4) Intracellular consecutive cysteine residues of LH receptor are palmitoylated and thereby inhibit internalization of the receptor. (5) As a mechanism of the bovine follicular cyst caused by stress, it is suggested that increased secretions of progesterone and cortisol from the adrenal gland exert inhibitory effects on the hypothalamus and follicle, respectively, and subsequently LH and FSH surges are blocked, then finally ovulation is suppressed and the follicle becomes cystic.

Molecular aspects of bovine cystic ovarian disease pathogenesis

“…Finally, ovulation does not occur and the follicle becomes cystic. This proposed mechanism agrees with the decreased expression of LHCGR reported both by Kawate (2004) and our group (Marelli et al 2014).…”

“…The gene encoding LHCGR contains 11 exons (Segaloff et al 1990, Segaloff & Ascoli 1993, while that encoding FSHR contains ten exons (Rajapaksha et al 1996, Hillier 2001. It has also been demonstrated that LHCGR and FSHR mRNAs are highly alternatively spliced (Figs 1 and 2; Rajapaksha et al 1996, Simoni et al 1997, Robert et al 2003, Kawate 2004, Nogueira et al 2010. However, there are no investigations of splice variants in ovarian follicular cysts.…”

Luteinizing hormone receptor splicing variants in bovine Leydig cells

“…Previous studies have shown that the variants with a partial deletion of exon 11 are translated into protein, but are not translocated to the cell membrane and instead become intracellularly trapped (Kawate, 2004). Thus, if these mRNAs are translated they are unable to bind LH and cannot activate adenylyl cyclase.…”

“…Under normal physiological conditions, testosterone is almost exclusively (>95%) of testicular origin (Wilson et al, 1981). Thus, the quality and quantity of LHR are important factors affecting the sensitivity to its ligand (Kawate, 2004).…”

“…Indeed, transcripts encoding alternatively spliced variants of the LHR have been detected in rat (Aatsinki et al, 1992), sheep (Bacich et al, 1994), horse ovary (Saint-Dizier et al, 2003), human corpus luteum (Nishimori et al, 1995), pig (Loosfelt et al, 1989), marmoset monkey (Michel et al, 2007), turkey (You et al, 2000), and cattle follicles (Robert et al, 2003). Although binding and functional properties of LHR splice variants have not been fully elucidated, it has been shown that the variants with a partial deletion of exon 11 are translated into protein, but not translocated to the cell membrane (Bacich et al, 1999;Kawate, 2004). In rats, deletion of the first 266 bp of exon 11 causes a frame shift in the reading frame and creates a truncated translation product.…”