Luteinizing hormone/ interstitial cell stimulating hormone (ICSH)

 

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Luteinizing hormone/ interstitial cell stimulating hormone (ICSH)

Introduction

Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In females, an acute rise of LH known as an LH surge, triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell stimulating hormone (ICSH), it stimulates Leydig cell production of testosterone. It acts synergistically with follicle-stimulating hormone (FSH). The term luteinizing comes from the Latin "luteus", meaning "yellow". This is in reference to the corpus luteum, which is a mass of cells that forms in an ovary after an ovum (egg) has been discharged. The corpus luteum is so named because it often has a distinctive yellow color. The process of forming the corpus luteum is known as "luteinization", and thus the hormone that triggers this process is termed the "luteinizing" hormone.

Structure

LH is a heterodimeric glycoprotein. Each monomeric unit is a glycoprotein molecule; one alpha and one beta subunit make the full, functional protein. Its structure is similar to that of the other glycoprotein hormones, follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and human chorionic gonadotropin (hCG).

The protein dimer contains 2 glycopeptidic subunits (labeled alpha- and beta- subunits) that are non-covalently associated:

The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids in human. The beta subunits vary. LH has a beta subunit of 120 amino acids (LHB) that confers its specific biologic action and is responsible for the specificity of the interaction with the LH receptor.

Functions

In both males and females, LH/ICSH works upon endocrine cells in the gonads to produce androgens.

Effects in females

LH supports theca cells in the ovaries that provide androgens and hormonal precursors for estradiol production. At the time of menstruation, FSH initiates follicular growth, specifically affecting granulosa cells. With the rise in estrogens, LH receptors are also expressed on the maturing follicle, which causes it to produce more estradiol. Eventually, when the follicle has fully matured, a spike in 17α-hydroxyprogesterone production by the follicle inhibits the production of estrogens. Previously, the preovulatory LH surge was attributed to a decrease in estrogen-mediated negative feedback of GnRH in the hypothalamus, subsequently stimulating the release of LH from the anterior pituitary. Some studies, however, attribute the LH surge to positive feedback from estradiol after production by the dominant follicle exceeds a certain threshold. 

Exceptionally high levels of estradiol induce hypothalamic production of progesterone, which stimulates elevated GnRH secretion, triggering a surge in LH. The increase in LH production only lasts for 24 to 48 hours. This "LH surge" triggers ovulation, thereby not only releasing the ovum from the follicle, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the endometrium for a possible implantation. LH is necessary to maintain luteal function for the second two weeks of the menstrual cycle. If pregnancy occurs, LH levels will decrease, and luteal function will instead be maintained by the action of hCG (human chorionic gonadotropin), a hormone very similar to LH but secreted from the new placenta.

Effects in males

ICSH acts upon the Leydig cells of the testis and is regulated by gonadotropin-releasing hormone (GnRH). The Leydig cells produce testosterone under the control of ICSH. ICSH binds to LH receptors on the membrane surface of Leydig cells. Binding to this receptor causes an increase in cyclic adenosine monophosphate (cAMP), a secondary messenger, which allows cholesterol to translocate into the mitochondria. Within the mitochondria, cholesterol is converted to pregnenolone by CYP11A1. Pregnenolone is then converted to dehydroepiandrosterone (DHEA). DHEA is then converted to androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD) and then finally converted to testosterone by 17β-hydroxysteroid dehydrogenase (HSD17B). The onset of puberty is controlled by two major hormones: FSH initiates spermatogenesis and ICSH signals the release of testosterone, an androgen that exerts both endocrine activity and intratesticular activity on spermatogenesis.

LH is released from the pituitary gland, and is controlled by pulses of gonadotropin-releasing hormone. When bloodstream testosterone levels are low, the pituitary gland is stimulated to release LH. As the levels of testosterone increase, it will act on the pituitary through a negative feedback loop and inhibit the release of GnRH and LH consequently. Androgens (including testosterone and dihydrotestosterone) inhibit monoamine oxidase (MAO) in the pineal gland, leading to increased melatonin and reduced LH and FSH by melatonin-induced increase of gonadotropin-inhibitory hormone (GnIH) synthesis and secretion. Testosterone can also be aromatized into estradiol (E2) to inhibit LH. E2 decreases pulse amplitude and responsiveness to GnRH from the hypothalamus onto the pituitary.

Changes in LH and testosterone blood levels and pulse secretions are induced by changes in sexual arousal in human males.

Effects in the brain

Luteinizing hormone receptors are located in areas of the brain associated with cognitive function. The role of LH role in the central nervous system (CNS) may be of relevance to understanding and treating post-menopausal cognitive decline.

Normal levels

During reproductive years, typical levels are between 1 and 20 IU/L. Physiologic high LH levels are seen during the LH surge (v.s.) and typically last 48 hours. In males over 18 years of age, reference ranges have been estimated to be 1.8–8.6 IU/L.

LH is measured in international units (IU). When quantifying the amount of LH in a sample in IUs, it is important to know which international standard your lot of LH was calibrated against since they can vary broadly from year to year. For human urinary LH, one IU is defined as 1/189th of an ampule denoted 96/602 and distributed by the NIBSC, corresponding to approximately 0.04656 μg of LH protein for a single IU, but older standard versions are still widely in use.