Luteinizing hormone

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Luteinizing hormone (LH, also known as luteinising hormone,

anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus.[3] In females, an acute rise of LH known as an LH surge, triggers ovulation[4] and development of the corpus luteum. In males, where LH had also been called interstitial cell–stimulating hormone (ICSH),[5] it stimulates Leydig cell production of testosterone.[4] It acts synergistically with follicle-stimulating hormone (FSH
).

Etymology

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 but remains unfertilized. 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:[6]

The different composition of these oligosaccharides 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).[citation needed] The biological half-life of LH is 23 hours subcutaneous[7] or terminal half life of 10-12 hours.[8]

Genes

The gene for the alpha subunit is located on chromosome 6q12.21.

The luteinizing hormone beta subunit gene is localized in the LHB/CGB gene cluster on

activin, and sex hormones
do not affect genetic activity for the beta subunit production of LH.

Function

Effects of LH on the body

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

Effects in females

LH supports

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.

Gonadal steroids (

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.[12]

Effects in males

LH acts upon the

17β-hydroxysteroid dehydrogenase (HSD17B). The onset of puberty is controlled by two major hormones: FSH initiates spermatogenesis and LH signals the release of testosterone,[17] 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.[13] 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.[18] 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)[19] 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.[20]

Changes in LH and testosterone blood levels and pulse secretions are induced by changes in sexual arousal in human males.[21]

Effects in the brain

Luteinizing hormone receptors are located in areas of the brain associated with

cognitive function.[22] The role of LH role in the central nervous system (CNS) may be of relevance to understanding and treating post-menopausal cognitive decline.[23]

Recent research has observed an inverse relationship between circulating LH and CNS LH levels.[24] After ovariectomy (a procedure used to mimic menopause) in female mice, circulating LH levels surge while CNS levels of LH fall.[25] Treatments that lower circulating LH restore LH levels in the CNS.[25]

Normal levels

Reference ranges for the blood content of luteinizing hormone (LH) during the menstrual cycle.[26]
  • The ranges denoted By biological stage may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
  • The ranges denoted Inter-cycle variability are more appropriate to use in non-monitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.
  • The ranges denoted Inter-woman variability are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.

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.[27]

LH is measured in

NIBSC, corresponding to approximately 0.04656 µg of LH protein for a single IU, but older standard versions are still widely in use.[28][29]

Lateral flow test strip for urine LH, used to predict ovulation

Predicting ovulation

Chance of fertilization by menstrual cycle day relative to ovulation[30]

The detection of a surge in release of luteinizing hormone indicates impending

conceiving.[32]

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.[33] On the other hand, the Chinese company Nantong Egens Biotechnology recommends using their test twice per day.[34] 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,[35] and recommendations of what time in the day to take the test varies between manufacturers and healthcare workers.[36] 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

fertility monitor.[medical citation needed
]

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).[citation needed
]

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.[citation needed
]

Disease states

Excess

In children with precocious puberty of pituitary or central origin, LH and FSH levels may be in the reproductive range instead of the low levels typical for their age.

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:

  1. Premature menopause
  2. Gonadal dysgenesis, Turner syndrome, Klinefelter syndrome
  3. Castration
  4. Swyer syndrome
  5. Polycystic ovary syndrome
  6. Certain forms of congenital adrenal hyperplasia
  7. Testicular failure
  8. Pregnancy – BetaHCG can mimic LH so tests may show elevated LH

Note: A medical drug for inhibiting luteinizing hormone secretion is butinazocine.[37]

Deficiency

Diminished secretion of LH can result in failure of gonadal function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. In females, amenorrhea is commonly observed. Conditions with very low LH secretions include:

  1. Pasqualini syndrome[38][39]
  2. Kallmann syndrome
  3. Hypothalamic suppression
  4. Hypopituitarism
  5. Eating disorder
  6. Female athlete triad
  7. Hyperprolactinemia
  8. Hypogonadism
  9. Gonadal suppression therapy
    1. GnRH antagonist
    2. GnRH agonist
      (inducing an initial stimulation (flare up) followed by permanent blockage of the GnRH pituitary receptor)

As a medication

LH is available mixed with FSH in the form of

IVF
therapy.

Often, HCG medication is used as an LH substitute because it activates the same receptor. Medically used hCG is derived from urine of pregnant women, is less costly, and has a longer half-life than LH.

Role in phosphorylation

steroidogenic cells of the ovary.[41]

References

  1. ^ GCSE Science Revision Biology "The Menstrual Cycle", retrieved 2022-03-23
  2. PMID 1498420
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  4. ^ a b Nosek TM. "Section 5/5ch9/s5ch9_5". Essentials of Human Physiology. Archived from the original on 2016-03-24.
  5. PMID 1122882
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  9. ^ Bowen R (13 May 2004). "Gonadotropins: Luteinizing and Follicle Stimulating Hormones". Colorado State University. Retrieved 12 March 2012.
  10. PMID 22028409
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  18. .
  19. .
  20. .
  21. .
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  25. ^ .
  26. .
  27. ^ "Test ID: LH, Luteinizing Hormone (LH), Serum". Mayo Medical Laboratories. Archived from the original on 2016-09-25. Retrieved 1 December 2012.
  28. ^ WHO Expert Committee on Biological Standardization (2003). "Proposed International Standard for Luteinizing Hormone" (PDF). Geneva: World Health Organization.
  29. ^ "WHO International Standard, Luteinizing Hormone, Human, Recombinant" (PDF). National Institute for Biological Standards and Control.
  30. PMID 10402400
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  31. .
  32. ^ "Ovulation Predictor Kit Frequently Asked Questions". Fertility Plus. Archived from the original on March 12, 2012. Retrieved 12 March 2012.[unreliable medical source?]
  33. ^ "Clear Blue Ovulation Test Instructions". Ovulation Guide. Retrieved 2018-01-19.
  34. ^ "Advanced Ovulation Test" (PDF). Homehealth-UK. Retrieved 2018-01-19. Version 1.1 02/11/15
  35. PMID 8059611
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  36. ^ Meniru GI (2001). Cambridge Guide to Infertility Management and Assisted Reproduction. Cambridge University Press. p. 67.
  37. ^ US 4406904, Welle HB, Marko M, "Method of inhibiting luteinizing hormone secretion with 6,7-benzomorphan derivatives", issued 27 September 1983, assigned to ACF Chemiefarma NV. 
  38. PMID 1727547
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  40. ^ "Luveris information". Archived from the original on June 18, 2006.[unreliable medical source?]
  41. PMID 32077149
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