Luteinizing hormone

Luteinizing hormone (LH, also known as lutropin and

Chorionic gonadotropin
sometimes lutrophin[1]) is a hormone produced by gonadotropic
alpha
cells in the anterior pituitary gland. In females, an acute rise of
LH ("LH surge") triggers ovulation[2] and development of the Identifiers
corpus luteum. In males, where LH had also been called Symbol CGA
interstitial cell–stimulating hormone (ICSH),[3] it stimulates Alt. HCG, GPHa, GPHA1
Leydig cell production of testosterone.[2] It acts synergistically symbols
with FSH.
NCBI 1081 (https://www.ncbi.nl
gene m.nih.gov/gene?cmd=retr
ieve&dopt=default&list_ui
Contents ds=1081&rn=1)
HGNC 1885 (https://www.genen
Structure
ames.org/data/gene-sym
Genes bol-report/#!/hgnc_id/HG
Function NC:1885)
Effects in females OMIM 118850 (https://omim.org/
Effects in males 118850)
Normal levels RefSeq NM_000735 (https://geno
Predicting ovulation me.ucsc.edu/cgi-bin/hgTr
Disease states acks?Submit=Submit&po
Excess sition=NM_000735&rn=1)
Deficiency UniProt P01215 (https://www.unip
rot.org/uniprot/P01215)
As a medication
Other data
References
Locus Chr. 6 q14-q21 (https://o
External links
mim.org/search/?index=g
eneMap&search=6q14)

Structure Luteinizing hormone beta

LH is a heterodimeric glycoprotein. Each monomeric unit is a polypeptide
glycoprotein molecule; one alpha and one beta subunit make the Identifiers
full, functional protein.
Symbol LHB
Its structure is similar to that of the other glycoprotein hormones, NCBI 3972 (https://www.ncbi.nl
follicle-stimulating hormone (FSH), thyroid-stimulating hormone gene m.nih.gov/gene?cmd=retri
(TSH), and human chorionic gonadotropin (hCG). The protein eve&dopt=default&list_uid
dimer contains 2 glycopeptidic subunits, labeled alpha and beta s=3972&rn=1)
subunits, that are non-covalently associated (i.e., without any HGNC 6584 (https://www.genena
disulfide bridge linking them):[4] mes.org/data/gene-symbol
-report/#!/hgnc_id/HGNC:6
The alpha subunits of LH, FSH, TSH, and hCG are
584)
identical, and contain 92 amino acids in human but 96
amino acids in almost all other vertebrate species OMIM 152780 (https://omim.org/
(glycoprotein hormones do not exist in invertebrates).
 The beta subunits vary. LH has a beta subunit of 120 152780)
amino acids (LHB) that confers its specific biologic RefSeq NM_000894 (https://geno
action and is responsible for the specificity of the
me.ucsc.edu/cgi-bin/hgTra
interaction with the LH receptor. This beta subunit
contains an amino acid sequence that exhibits large cks?Submit=Submit&positi
homologies with that of the beta subunit of hCG and on=NM_000894&rn=1)
both stimulate the same receptor. However, the hCG UniProt P01229 (https://www.unipr
beta subunit contains an additional 24 amino acids, and
ot.org/uniprot/P01229)
the two hormones differ in the composition of their
sugar moieties. Other data
The different composition of these oligosaccharides affects Locus Chr. 19 q13.3 (https://omi
bioactivity and speed of degradation. The biologic half-life of LH m.org/search/?index=gene
is 20 minutes, shorter than that of FSH (3–4 hours) and hCG (24 Map&search=19q13.3)
hours). The biological half-life of LH is 23 hours subcutaneous[5]
or terminal half life of 10-12 hours.[6]

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 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.

Function
In females: ovulation, maintaining of corpus luteum and secretion of progesterone.

In males: testosterone secretion.

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.[7] 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, 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.[8] However another theory of the LH peak is a positive feedback
mechanism from estradiol. The levels keep rising through the follicular phase and when they reach an
unknown threshold, this results in the peak of the LH.[9] This effect is opposite from the usual negative
feedback mechanism presented at lower levels. In other words, the mechanism(s) are not yet clear. The
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 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 of LH on the body

Gonadal steroids (estrogens 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.[10]

Effects in males
LH acts upon the Leydig cells of the testis and is regulated by gonadotropin-releasing hormone
(GnRH).[11] The Leydig cells produce testosterone (T) under the control of LH, which regulates the
expression of the enzyme 17β-hydroxysteroid dehydrogenase that is used to convert androstenedione, the
hormone produced by the testes, to testosterone. The onset of puberty is controlled by two major
hormones: FSH initiates spermatogenesis and LH 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 T levels are low, it stimulating the pituitary gland to release LH.[11] As the levels of T increase, it
will act on the pituitary through a negative feedback loop and inhibit the release of GnRH and LH
consequently. Androgens (T, DHT) inhibit monoamine oxidase (MAO) in pineal, leading to increased
melatonin and reduced LH and FSH by melatonin-induced increase of Gonadotropin-Inhibitory Hormone
(GnIH)[12] synthesis and secretion. T can also be aromatized into estradiol (E2) to inhibit LH. E2
decreases pulse amplitude and responsiveness to GnRH from the hypothalamus onto the pituitary.[13]

Changes in LH and testosterone (T) blood levels and pulse secretions are induced by changes in sexual
arousal in human males.[14]

Normal levels
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 proper information about
its blood level.
Reference ranges for the blood content of luteinizing hormone (LH) during
During the reproductive the menstrual cycle.[15]
years, typical levels are
between 1–20 IU/L. The ranges denoted By biological stage may be used in
Physiologic high LH levels closely monitored menstrual cycles in regard to other
are seen during the LH surge markers of its biological progression, with the time scale
(v.s.); typically they last 48 being compressed or stretched to how much faster or
hours. slower, respectively, the cycle progresses compared to an
average cycle.
In males over 18 years of age,
The ranges denoted Inter-cycle variability are more
reference ranges have been
estimated to be 1.8–8.6 appropriate to use in non-monitored cycles with only the
IU/L.[16] beginning of menstruation known, but where the woman
accurately knows her average cycle lengths and time of
LH is measured in ovulation, and that they are somewhat averagely regular,
international units (IU). with the time scale being compressed or stretched to how
When quantifying the amount much a woman's average cycle length is shorter or longer,
of LH in a sample in IUs, it is respectively, than the average of the population.
important to know which The ranges denoted Inter-woman variability are more
international standard your
appropriate to use when the average cycle lengths and time
lot of LH was calibrated
of ovulation are unknown, but only the beginning of
against, as they can vary
menstruation is given.
broadly from year to year.
For human urinary LH, one
IU is most recently defined as 1/189th of an ampule denoted 96/602 and distributed by the NIBSC,
corresponding to approximately 0.04656µg of LH protein for a single IU, but older standard versions are
still widely in use.[17][18]

Predicting ovulation
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.[20] 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 intention of conceiving.[21]

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.[22] On the other hand, the Chinese company Nantong
Egens Biotechnology recommends using their test twice per
day.[23] 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,[24] and recommendations of what
time in the day to take the test varies between manufacturers and
Chance of fertilization by menstrual
healthcare workers.[25] Tests may be read manually using a color-
cycle day relative to ovulation.[19]
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
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
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.[26]

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[27][28][29]
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 menotropin, 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).[30] 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
1. Ujihara M, Yamamoto K, Nomura K, Toyoshima S, Demura H, Nakamura Y, Ohmura K,
 Osawa T (June 1992). "Subunit-specific sulphation of oligosaccharides relating to charge-
heterogeneity in porcine lutrophin isoforms". Glycobiology. 2 (3): 225–31.
doi:10.1093/glycob/2.3.225 (https://doi.org/10.1093%2Fglycob%2F2.3.225). PMID 1498420
(https://pubmed.ncbi.nlm.nih.gov/1498420).
2. Nosek, Thomas M. Essentials of Human Physiology. Section 5/5ch9/s5ch9_5
3. Louvet JP, Harman SM, Ross GT (May 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 (https://doi.org/10.1210%2Fe
ndo-96-5-1179). PMID 1122882 (https://pubmed.ncbi.nlm.nih.gov/1122882).
4. Jiang X, Dias JA, He X (January 2014). "Structural biology of glycoprotein hormones and
their receptors: insights to signaling". Molecular and Cellular Endocrinology. 382 (1): 424–
51. doi:10.1016/j.mce.2013.08.021 (https://doi.org/10.1016%2Fj.mce.2013.08.021).
PMID 24001578 (https://pubmed.ncbi.nlm.nih.gov/24001578).
5. Ezcurra D, Humaidan P (October 2014). "A review of luteinising hormone and human
chorionic gonadotropin when used in assisted reproductive technology" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC4287577). Reproductive Biology and Endocrinology. 12 (1): 95.
doi:10.1186/1477-7827-12-95 (https://doi.org/10.1186%2F1477-7827-12-95).
PMC 4287577 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287577). PMID 25280580
(https://pubmed.ncbi.nlm.nih.gov/25280580).
6. le Cotonnec JY, Porchet HC, Beltrami V, Munafo A (February 1998). "Clinical pharmacology
of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous
administration to healthy female volunteers and comparison with urinary human luteinizing
hormone". Fertility and Sterility. 69 (2): 189–94. doi:10.1016/S0015-0282(97)00501-3 (http
s://doi.org/10.1016%2FS0015-0282%2897%2900501-3). PMID 9496327 (https://pubmed.nc
bi.nlm.nih.gov/9496327).
7. Bowen R (13 May 2004). "Gonadotropins: Luteinizing and Follicle Stimulating Hormones" (h
ttp://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/lhfsh.html). Colorado State
University. Retrieved 12 March 2012.
8. Mahesh VB (January 2012). "Hirsutism, virilism, polycystic ovarian disease, and the steroid-
gonadotropin-feedback system: a career retrospective" (https://www.ncbi.nlm.nih.gov/pmc/a
rticles/PMC3328092). American Journal of Physiology. Endocrinology and Metabolism. 302
(1): E4–E18. doi:10.1152/ajpendo.00488.2011 (https://doi.org/10.1152%2Fajpendo.00488.2
011). PMC 3328092 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328092).
PMID 22028409 (https://pubmed.ncbi.nlm.nih.gov/22028409).
9. Guyton and Hall Textbook of Medical Physiology 2006 page 1021
10. Norris DO, Carr JA (2013). Vertebrate Endocrinology (https://books.google.com/books?id=F
_NaW1ZcSSAC&printsec=frontcover#v=onepage&q&f=false). Academic Press. p. 126.
ISBN 978-0-12-396465-6.
11. "Male Medical Fertility Treatment: HCG + LH + Recombinant FSH To Increase Sperm Count
Through Spermatogenisis" (https://web.archive.org/web/20150219164931/http://www.testos
teronetherapy.com/low_testosterone_treatment/male-fertility-treatment-hcg-lh-recombinant-f
sh.html). Archived from the original (http://www.testosteronetherapy.com/low_testosterone_t
reatment/male-fertility-treatment-hcg-lh-recombinant-fsh.html) on February 19, 2015.
Retrieved 6 April 2015.
12. Ubuka T, Son YL, Tobari Y, Narihiro M, Bentley GE, Kriegsfeld LJ, Tsutsui K (2014). "Central
and Direct Regulation of Testicular Activity by Gonadotropin-Inhibitory Hormone and Its
Receptor" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902780). Frontiers in
Endocrinology. 5: 8. doi:10.3389/fendo.2014.00008 (https://doi.org/10.3389%2Ffendo.2014.
00008). PMC 3902780 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902780).
PMID 24478760 (https://pubmed.ncbi.nlm.nih.gov/24478760).
13. Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF, Hayes FJ (March
2008). "Inhibition of luteinizing hormone secretion by testosterone in men requires
aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem
study of normal and gonadotropin-releasing hormone-deficient men" (https://www.ncbi.nlm.n
ih.gov/pmc/articles/PMC2266963). The Journal of Clinical Endocrinology and Metabolism.
93 (3): 784–91. doi:10.1210/jc.2007-2156 (https://doi.org/10.1210%2Fjc.2007-2156).
PMC 2266963 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266963). PMID 18073301
(https://pubmed.ncbi.nlm.nih.gov/18073301).
14. Stoléru SG, Ennaji A, Cournot A, Spira A (1993). "LH pulsatile secretion and testosterone
blood levels are influenced by sexual arousal in human males". Psychoneuroendocrinology.
18 (3): 205–18. doi:10.1016/0306-4530(93)90005-6 (https://doi.org/10.1016%2F0306-453
0%2893%2990005-6). PMID 8516424 (https://pubmed.ncbi.nlm.nih.gov/8516424).
15. Häggström M (2014). "Reference ranges for estradiol, progesterone, luteinizing hormone
and follicle-stimulating hormone during the menstrual cycle". WikiJournal of Medicine. 1 (1).
doi:10.15347/wjm/2014.001 (https://doi.org/10.15347%2Fwjm%2F2014.001). ISSN 2002-
4436 (https://www.worldcat.org/issn/2002-4436).
16. Mayo Medical Laboratories - Test ID: LH, Luteinizing Hormone (LH), Serum (http://www.may
omedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8663), retrieved December
2012
17. World Health Organization Proposed International Standard for Luteinizing Hormone. (http://
apps.who.int/iris/bitstream/10665/68388/1/WHO_BS_03.1983.pdf) WHO Expert Committee
on Biological Standardization. World Health Organization. Geneva. 2003.
18. WHO International Standard, Luteinizing Hormone, Human, Recombinant. (http://www.nibs
c.org/documents/ifu/96-602.pdf) National Institute for Biological Standards and Control.
19. Dunson DB, Baird DD, Wilcox AJ, Weinberg CR (July 1999). "Day-specific probabilities of
clinical pregnancy based on two studies with imperfect measures of ovulation". Human
Reproduction. 14 (7): 1835–9. doi:10.1093/humrep/14.7.1835 (https://doi.org/10.1093%2Fh
umrep%2F14.7.1835). PMID 10402400 (https://pubmed.ncbi.nlm.nih.gov/10402400).
20. Nielsen MS, Barton SD, Hatasaka HH, Stanford JB (August 2001). "Comparison of several
one-step home urinary luteinizing hormone detection test kits to OvuQuick". Fertility and
Sterility. 76 (2): 384–7. doi:10.1016/S0015-0282(01)01881-7 (https://doi.org/10.1016%2FS0
015-0282%2801%2901881-7). PMID 11476792 (https://pubmed.ncbi.nlm.nih.gov/1147679
2).
21. "Ovulation Predictor Kit Frequently Asked Questions" (https://web.archive.org/web/2012031
2021506/http://www.pinelandpress.com/faq/opk.html). Fertility Plus. Archived from the
original (http://www.pinelandpress.com/faq/opk.html) on March 12, 2012. Retrieved
12 March 2012.
22. "Clear Blue Ovulation Test Instructions" (http://ovulation.guide/clear-blue-ovulation-test-instr
uctions/). Ovulation Guide. Retrieved 2018-01-19.
23. "Advanced Ovulation Test" (https://homehealth-uk.com/wp/wp-content/uploads/2015/12/ME
G_ADV_egens_3.5mm_one_step_LH_strip_v1.1_02.11.15.pdf) (PDF). Homehealth-UK.
Retrieved 2018-01-19. Version 1.1 02/11/15
24. Martinez AR, Bernardus RE, Vermeiden JP, Schoemaker J (1994). "Time schedules of
intrauterine insemination after urinary luteinizing hormone surge detection and pregnancy
results". Gynecol Endocrinol. 8 (1): 1–5. doi:10.3109/09513599409028450 (https://doi.org/1
0.3109%2F09513599409028450). PMID 8059611 (https://pubmed.ncbi.nlm.nih.gov/805961
1).
25. Page 67 (https://books.google.se/books?id=upuEMZPvVIwC&pg=PA67) in: Godwin I.
Meniru (2001). Cambridge Guide to Infertility Management and Assisted Reproduction.
Cambridge University Press.
26. U.S. Patent 4,406,904 (https://www.google.com/patents/US4406904)
27. Weiss J, Axelrod L, Whitcomb RW, Harris PE, Crowley WF, Jameson JL (January 1992).
"Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing
hormone". The New England Journal of Medicine. 326 (3): 179–83.
doi:10.1056/NEJM199201163260306
(https://doi.org/10.1056%2FNEJM199201163260306). PMID 1727547 (https://pubmed.ncbi.
nlm.nih.gov/1727547).
28. Valdes-Socin H, Salvi R, Daly AF, Gaillard RC, Quatresooz P, Tebeu PM, Pralong FP,
Beckers A (December 2004). "Hypogonadism in a patient with a mutation in the luteinizing
hormone beta-subunit gene" (http://orbi.ulg.ac.be/handle/2268/23485). The New England
Journal of Medicine. 351 (25): 2619–25. doi:10.1056/NEJMoa040326 (https://doi.org/10.105
6%2FNEJMoa040326). PMID 15602022 (https://pubmed.ncbi.nlm.nih.gov/15602022).
29. Valdes-Socin H, Daly AF, Beckers A (2017). "Luteinizing Hormone Deficiency: Historical
Views and Future Perspectives" (http://austinpublishinggroup.com/andrology/download.ph
p?file=fulltext/andrology-v2-id1015.pdf) (PDF). Austin Andrology. 2 (1): 1015.
30. Luveris information (http://www.fertilitylifelines.com/serono/products/luveris/index.jsp)
Archived (https://web.archive.org/web/20060618151316/http://www.fertilitylifelines.com/sero
no/products/luveris/index.jsp) June 18, 2006, at the Wayback Machine

External links
Luteinizing+Hormone (https://meshb.nlm.nih.gov/record/ui?name=Luteinizing%20Hormone)
at the US National Library of Medicine Medical Subject Headings (MeSH)

Retrieved from "https://en.wikipedia.org/w/index.php?title=Luteinizing_hormone&oldid=937565882"

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