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).
Etymology
Structure
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 but 96 amino acids in almost all other vertebrate species (glycoprotein hormones do not exist in invertebrates).
- 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. This beta subunit contains an amino acid sequence that exhibits large homologies with that of the beta subunit of hCG and both stimulate the same receptor. However, the hCG beta subunit contains an additional 24 amino acids, and the two hormones differ in the composition of their sugar moieties.
The different composition of these affects bioactivity and speed of degradation. The biologic half-life of LH is 20 minutes, shorter than that of FSH (3–4 hours) and hCG (24 hours). The biological half-life of LH is 23 hours subcutaneous or terminal half life of 10-12 hours.
Genes
The luteinizing hormone beta subunit gene is localized in the LHB/CGB gene cluster on chromosome 19q13.32. In contrast to the alpha gene activity, beta LH subunit gene activity is restricted to the pituitary gonadotropic cells. It is regulated by the gonadotropin-releasing hormone from the hypothalamus. GnRH activates Egr1 which interacts with transcription factors NR5A1 and PITX1 at the gene promoter to up-regulate LHB transcription.
Function
Effects in females
Gonadal steroids (oestrogen and androgens) generally have negative feedback effects on GnRH-1 release at the level of the hypothalamus and at the gonadotropes, reducing their sensitivity to GnRH. Positive feedback by estrogens also occurs in the gonadal axis of female mammals and is responsible for the midcycle surge of LH that stimulates ovulation. Although estrogens inhibit kisspeptin (Kp) release from kiss1 neurons in the ARC, estrogens stimulate Kp release from the Kp neurons in the AVPV. As estrogens' levels gradually increase the positive effect predominates, leading to the LH surge. GABA-secreting neurons that innervate GnRH-1 neurons also can stimulate GnRH-1 release. These GABA neurons also possess ERs and may be responsible for the GnRH-1 surge. Part of the inhibitory action of endorphins on GnRH-1 release is through inhibition of these GABA neurons. Rupture of the ovarian follicle at ovulation causes a drastic reduction in estrogen synthesis and a marked increase in secretion of progesterone by the corpus luteum in the ovary, reinstating a predominantly negative feedback on hypothalamic secretion of GnRH-1.
Effects in males
LH is released from the pituitary gland, and is controlled by pulses of GnRH. 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
Some research has observed an inverse relationship between circulating LH and CNS LH levels. After ovariectomy (a procedure used to mimic menopause) in female mice, circulating LH levels surge while CNS levels of LH fall. Treatments that lower circulating LH restore LH levels in the CNS.
Normal levels
LH levels are normally low during childhood and in women, high after menopause. Since LH is secreted as pulses, it is necessary to follow its concentration over a sufficient period of time to get proper information about its blood level.
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.
Predicting ovulation
The recommended testing frequency differs between manufacturers. For example, the Clearblue test is taken daily, and an increased frequency does not decrease the risk of missing an LH surge. On the other hand, the Chinese company Nantong Egens Biotechnology recommends using their test twice per day. Version 1.1 02/11/15 If testing once per day, no significant difference has been found between testing LH in the morning versus in the evening, in relation to conception rates, and recommendations of what time in the day to take the test varies between manufacturers and healthcare workers. Tests may be read manually using a color-change paper strip, or digitally with the assistance of reading electronics.
Tests for luteinizing hormone may be combined with testing for estradiol in tests such as the Clearblue fertility monitor.
The sensitivity of LH tests are measured in milli international unit, with tests commonly available in the range 10–40 m.i.u. (the lower the number, the higher the sensitivity).
As sperm can stay viable in the woman for several days, LH tests are not recommended for contraceptive practices, as the LH surge typically occurs after the beginning of the fertile window.
Disease states
Excess
During the reproductive years, relatively elevated LH is frequently seen in patients with polycystic ovary syndrome; however, it would be unusual for them to have LH levels outside of the normal reproductive range.
Persistently high LH levels are indicative of situations where the normal restricting feedback from the gonad is absent, leading to a pituitary production of both LH and FSH. While this is typical in menopause, it is abnormal in the reproductive years. There it may be a sign of:
- Premature menopause
- Gonadal dysgenesis, Turner syndrome, Klinefelter syndrome
- Castration
- Swyer syndrome
- Polycystic ovary syndrome
- Certain forms of congenital adrenal hyperplasia
- Testicular failure
- Pregnancy – BetaHCG can mimic LH so tests may show elevated LH
Note: A medical drug for inhibiting luteinizing hormone secretion is butinazocine.
Deficiency
- Pasqualini syndrome
- Kallmann syndrome
- Hypothalamic suppression
- Hypopituitarism
- Eating disorder
- Female athlete triad
- Hyperprolactinemia
- Hypogonadism
- Gonadal suppression therapy
- GnRH antagonist
- GnRH agonist (inducing an initial stimulation (flare up) followed by permanent blockage of the GnRH pituitary receptor)
As a medication
Role in phosphorylation
External links
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