An Overview of the Past, Present, and Future of Nongonadal LH/hCG Actions in Reproductive Biology and Medicine

Abstract

Even though there were hints, it was not until 1986 that a number of laboratories worldwide began to demonstrate unequivocally the presence and functions of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors in various female and male nongonadal tissues. There was no species specificity but there was tissue specificity in the nongonadal LH/hCG receptor distribution. Nongonadal receptor levels were lower but they were regulated and processed and used signaling mechanisms similarly to gonadal receptors. Although still greater understanding is needed, gains made in the last decade demonstrate that nongonadal actions of LH/hCG are physiologically important and may have relevance to better understanding several diseases and their treatment. A recently developed LH receptor knockout model has begun to reaffirm and extend the importance of nongonadal LH signaling in the body.

Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin

“…Similarly, in healthy middle-aged men, urinary hCG does not acutely alter circulating leptin (86). Hence, the lack of effect of r-hCG on leptin may be specific to gonadotropins (87). Similarly, testosterone increases IGF-I in young and old, eugonadal and hypogonadal men (23,88,89), but nandrolone does not (89).…”

Could bone tissue be a target for luteinizing hormone/chorionic gonadotropin?

“…Since both LHRH agonists and OVX result in estrogen deficiency it was tempting to explain the differences observed for OH-Pro on LH status. Such a possibility was supported in a subsequent examination of the literature that indicated that receptors for LH were being reported for many estrogen sensitive extragonadal sites (Rao, 2001). Skeletal metabolism undergoes significant changes during puberty, pregnancy and the menopause and although considerable attention has been ascribed to the role played by sex steroids during these periods, the interaction of the gonadotropin hormones, LH and hCG within bone tissue have been overlooked.…”

“…Receptors for LH have been identified in many extragonadal sites (Rao 2001), furthermore there is a compelling relationship between LH receptor expression and the sensitivity of the same site to oestrogen (Gawronska et al 1999) and expression of LH receptors has been linked to changes in oestrogen status in several species (Gawronska et al 1999;Akazome and Mori 1999;Knecht et al, 1984). Since bone-forming osteoblasts have been found to express receptors for estrogen (Komm et al 1988, Eriksen et al 1988) it was also a possibility that these same cells might also express receptors for LH.…”

“…Both LH and hCG bind to the same receptor, a seven transmembrane domain G-protein coupled receptor (Dufau, 1998) that is assuming a greater global significance in the regulation of tissue metabolism than was once thought. The identification of receptors for LH outside of the ovarian-pituitary axis is relatively recent (Rao, 2001). Interestingly there is a compelling association between LH receptor expression and the sensitivity of the same site to estrogen.…”

Human chorionic gonadotropin prevents Sjögren's syndrome–like exocrinopathy in mice

“…However, there is growing evidence that HCG can also act directly as an immune modulator (8,16), because its receptors are widely distributed in nongonadal tissue, including immune cells (17). Either mechanism or the additive effects of both mechanisms could produce the same end result, i.e., immunosuppression preventing autoimmune exocrinopathy in NOD mice.…”