Luteinizing hormone

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Luteinizing hormone beta polypeptide
Figure 28 03 01.jpg
Effects of LH on the body
Identifiers
Symbol LHB
Entrez 3972
HUGO 6584
OMIM 152780
RefSeq NM_000894
UniProt P01229
Other data
Locus Chr. 19 q13.3

Luteinizing hormone (LH, also known as lutropin[1] and sometimes lutrophin[2]) is a hormone produced by gonadotroph cells in the anterior pituitary gland. In females, an acute rise of LH ("LH surge") triggers ovulation[3] and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone (ICSH),[4] it stimulates Leydig cell production of testosterone.[3] It acts synergistically with FSH.

Structure[edit]

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 (i.e., without any disulfide bridge linking them):[5]

  • 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 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]

Reference ranges for the blood content of luteinizing hormone (LH) during the menstrual cycle. * 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.

Genes[edit]

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

Activity[edit]

In both males and females, LH is essential for reproduction.

  • 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.[6] 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 17-hydroxyprogesterone production by the follicle inhibits the production of estrogen, leading to a decrease in estrogen-mediated negative feedback of GnRH in the hypothalamus, which then stimulates the release of LH from the anterior pituitary.[7] This increase in LH production only lasts for 24 to 48 hours. This "LH surge" triggers ovulation, thereby not only releasing the egg 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 first 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).
  • In males, LH acts upon the Leydig cells of the testis and is regulated by GnRH.[8] The Leydig cells produce testosterone (T) under the control of LH, which regulates the expression of the enzyme 17-β hydroxysteroid dehydrogenase that is used to convert androstenedione, the hormone produced by the gonads, to testosterone,[9] 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 (GnRH). When T levels are low, GnRH is released by the hypothalamus, stimulating the pituitary gland to release LH.[10] As the levels of T increase, it will act on the hypothalamus and pituitary through a negative feedback loop and inhibit the release of GnRH and LH consequently.[11] However, T must first be aromatized into Estradiol (E2) in order to inhibit LH. E2 decreases pulse amplitude and responsiveness to GnRH from the hypothalamus onto the pituitary.[12]

Changes in LH and testosterone (T) blood levels and pulse secretions are induced by changes in sexual arousal in human males.[13]

Normal levels[edit]

LH levels are normally low during childhood and, in women, high after menopause. As LH is secreted as pulses, it is necessary to follow its concentration over a sufficient period of time to get a proper information about its blood level.

During the reproductive years, typical levels are between 1-20 IU/L. Physiologic high LH levels are seen during the LH surge (v.s.); typically they last 48 hours.

In males over 18 years of age, reference ranges have been estimated to be 1.8-8.6 IU/L.[14]

LH is measured in International Units (IU). For Human Urinary LH, one IU is defined as the amount of LH that has an activity corresponding to 0.13369 mg of pure Human Urinary LH.[15]

Ovulatietest.jpg

Predicting ovulation[edit]

The detection of a surge in release of luteinizing hormone indicates impending ovulation. LH can be detected by urinary ovulation predictor kits (OPK, also LH-kit) that are performed, typically daily, around the time ovulation may be expected.[16] A conversion from a negative to a positive reading would suggest that ovulation is about to occur within 24–48 hours, giving women two days to engage in sexual intercourse or artificial insemination with the intentions of conceiving.[17]

Tests may be read manually using a colour-change paper strip, or digitally with the assistance of reading electronics.

Tests for luteinising hormone may be combined with testing for estradiol in tests such as the Clearblue fertility monitor.[18]

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.

Disease states[edit]

Relative elevations[edit]

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 the polycystic ovary syndrome; however, it would be unusual for them to have LH levels outside of the normal reproductive range.

High LH levels[edit]

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 the menopause, it is abnormal in the reproductive years. There it may be a sign of:

  1. Premature menopause
  2. Gonadal dysgenesis, Turner 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

Deficient LH activity[edit]

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 are:

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

Availability[edit]

LH is available mixed with FSH in the form of Pergonal, and other forms of urinary gonadotropins . More purified forms of urinary gonadotropins may reduce the LH portion in relation to FSH. Recombinant LH is available as lutropin alfa (Luveris).[19] All these medications have to be given parenterally. They are commonly used in infertility therapy to stimulate follicular development, the notable one being in 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.

References[edit]

  1. ^ lutropin at eMedicine Dictionary
  2. ^ "Subunit-specific sulphation of oligosaccharides relating to chargeheterogeneity in porcine lutrophin isoforms". Oxford Journals. 1 February 1992. Retrieved 17 May 2012. 
  3. ^ a b Physiology at MCG 5/5ch9/s5ch9_5
  4. ^ Louvet J, Harman S, Ross G (1975). "Effects of human chorionic gonadotropin, human interstitial cell stimulating hormone and human follicle-stimulating hormone on ovarian weights in estrogen-primed hypophysectomized immature female rats". Endocrinology 96 (5): 1179–86. doi:10.1210/endo-96-5-1179. PMID 1122882. 
  5. ^ Jiang X, Dias JA, He X (Aug 2013). "Structural biology of glycoprotein hormones and their receptors: Insights to signaling". Mol Cell Endocrinol 382 (1): 424–51. doi:10.1016/j.mce.2013.08.021. PMID 24001578. 
  6. ^ Bowen, R. (13 May 2004). "Gonadotropins: Luteinizing and Follicle Stimulating Hormones". Colorado State University. Retrieved 12 March 2012. 
  7. ^ Mahesh, V. B. (25 October 2011). "Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective". AJP: Endocrinology and Metabolism 302 (1): E4-E18. doi:10.1152/ajpendo.00488.2011. PMID 22028409. 
  8. ^ http://www.testosteronetherapy.com/low_testosterone_treatment/male-fertility-treatment-hcg-lh-recombinant-fsh.html. Retrieved 20 November 2013.  Missing or empty |title= (help)
  9. ^ https://www.boundless.com/biology/mammalian-reproduction/hormones-in-the-male-reproductive-system/role-of-hormones-in-controlling-male-reproductive-system/. Retrieved 20 November 2013.  Missing or empty |title= (help)
  10. ^ http://www.testosteronetherapy.com/low_testosterone_treatment/male-fertility-treatment-hcg-lh-recombinant-fsh.html. Retrieved 20 November 2013.  Missing or empty |title= (help)
  11. ^ https://www.boundless.com/biology/mammalian-reproduction/hormones-in-the-male-reproductive-system/role-of-hormones-in-controlling-male-reproductive-system/. Retrieved 20 November 2013.  Missing or empty |title= (help)
  12. ^ . March 2008 http://jcem.endojournals.org/content/93/3/784.full. Retrieved 12 November 2013.  Missing or empty |title= (help)
  13. ^ Stoleru, S. (1993). "LH pulsatile secretion and testosterone blood levels are influenced by sexual arousal in human males". Psyconeuroendocrinology. Retrieved 12 November 2012. 
  14. ^ Mayo Medical Laboratories > Test ID: LH, Luteinizing Hormone (LH), Serum, retrieved December 2012
  15. ^ World Health Organization Technical Report Series N0. 565. WHO Expert Committee on Biological Standardization. Twenty-sixth Report. World Health Organization. Geneva. 1975
  16. ^ Nielsen M, Barton S, Hatasaka H, Stanford J (2001). "Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick". Fertil Steril 76 (2): 384–7. doi:10.1016/S0015-0282(01)01881-7. PMID 11476792. 
  17. ^ "Ovulation Predictor Kit Frequently Asked Questions". Fertility Plus. Retrieved 12 March 2012. 
  18. ^ "How to Get Pregnant". OPregnancy.com. 2009. Retrieved 12 March 2012. 
  19. ^ Luveris information

External links[edit]