In males, LH stimulates testosterone release by the Leydig cells of the testes. In females, LH stimulates steroid release from the ovaries, ovulation, and the release of progesterone after ovulation by the corpus luteum [8].

Ovulation

Ovulation is made possible due to the combined actions of the hypothalamus, pituitary, and ovary. The hypothalamus begins the process of ovulation by releasing GnRH in a pulsatile fashion. This pulsatile release causes the anterior pituitary to release LH and FSH, which then act on the ovarian follicle. This follicle is made up of 3 essential cells: theca cells, granulosa cells, and the oocyte. LH causes the theca cells to make androstenedione. Androstenedione then converts to estradiol via aromatase, which is stimulated by FSH. Upon achieving a critical concentration of estradiol, the negative feedback on LH that normally occurs by estrogen is shut off, and it begins to have positive feedback on LH release, which causes an “LH surge” which initiates ovulation. Once ovulation has occurred, the follicle becomes the corpus luteum. The corpus luteum secretes progesterone and is stimulated by LH or hCG if a pregnancy occurs [9].

Luteinizing hormone acts by binding to a G-protein coupled receptor, which in turn activates adenylyl cyclase. Adenylyl cyclase, an enzyme, then produces cyclic-AMP, thus increasing its intracellular concentration, which then activates a kinase molecule called protein kinase A (PKA). PKA then phosphorylates specific intracellular proteins that subsequently achieve the end physiological actions of LH like steroid production and ovulation [8].

Ovulation predictor kits are used by women to determine the exact time of ovulation while trying to get pregnant. These kits work by quantifying luteinizing hormone levels in the urine [10].

Testicular Dysfunction in Chronic Kidney Disease (CKD)

Low libido, potency, and testicular size are all signs of testicular dysfunction. In end-stage renal disease, all these signs can present. Testosterone concentration in the plasma and how quickly testosterone production takes place are usually low in patients with chronic kidney disease. Spermatogenesis has been noted to be either lowered or completely absent as well. After renal transplantation, the changes noted above can be reversed and return to normal. Studies have shown that this testicular dysfunction and altered testosterone concentration results from higher levels of LH in the plasma and lower amounts of secretory LH pulses seen in men with end-stage renal disease when compared to healthy subjects or men who underwent a successful renal transplant. This fact is significant because the pulsatile secretion of LH is necessary for gonadotropin receptors of the testes to function properly. Furthermore, sustained high levels of LH in the blood and testes can cause a loss of gonadotropin receptors in the testes [11].

Infertility and Assisted Reproductive Technology (ART)

Infertility is defined clinically as the inability to become clinically pregnant after at least 12 months of unprotected sexual intercourse. It can be caused by female factors, male factors, or both. In women, it can be the result of ovulatory issues (i.e., anovulation), obstructions of the fallopian tubes, and endometriosis. To become pregnant, many women undergo assisted reproductive technologies (ART), like intrauterine insemination and in vitro fertilization [12].

Proper development of a follicle and ovulation involves the combined effects of FSH and LH and their activities in the body. This interplay between FSH and LH has also been shown to be important in ART. It has been found that low LH levels in the body can result in poor outcomes in ART. Thus, patients who have low endogenous LH, such as with hypogonadotropic hypogonadism, can have an increase in efficacy of ART with exogenous LH treatment [13]. A further study found that with supplementation of LH during the mid-follicular phase, there were better pregnancy results in women who had not responded optimally to conventional ART. This outcome was thought to be due to the increased production of 17-beta-estradiol [2]. Another study reported that fertilization, implantation, and clinical pregnancy rates were all higher in patients who underwent ART that included the use of recombinant human LH (r-hLH) when compared to patients who underwent ART without the use of r-hLH. A lower apoptosis rate was also present in patients who underwent ART that included r-hLH [5].

Although there are demonstrable benefits of LH supplementation during ART, research also shows that levels of LH can have unfavorable effects on ART [13]. These adverse effects are thought to result from inhibition of granulosa cell proliferation, atresia of immature follicles, and luteinization of preovulatory follicles before they would be under physiological conditions. Besides, increased LH before ovulation has been shown to influence the conception and implantation of the embryo negatively [2].

Hypogonadotropic Hypogonadism in Males

Hypogonadism is impaired testicular function; this can occur due to a problem with the testes (primary/hypogonadotropic hypogonadism) or due to a problem with the hypothalamic-pituitary-gonadal axis (secondary/hypogonadotropic hypogonadism). Men with hypogonadotropic hypogonadism have low levels of androgens in the plasma as well as a lack or delay of sexual maturity, which can cause symptoms such as a lack of libido, depression, increase in adipose tissue, and diminished erectile function [14].

Patients with hypogonadotropic hypogonadism usually have an issue with GnRH signaling, which then causes a decrease in FSH and LH secretion. This decrease in FSH and LH contributes to both decreased androgen levels as well as reduced spermatogenesis. Studies have shown that giving these patients pulsatile GnRH or LH (or hCG) and FSH can help increase spermatogenesis and thus increase the sperm concentration in the ejaculate. Even then, most couples will need ART to achieve pregnancy [15].