Editing Luteinizing hormone (section)

== Function ==
[[File:Figure 28 03 01.jpg|thumb|Effects of LH on the body|500px]]

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

===Effects in females===

LH supports [[theca cell]]s in the ovaries that provide [[androgen]]s and hormonal precursors for [[estradiol]] production. At the time of [[menstruation]], FSH initiates [[Ovarian follicle|follicular]] growth, specifically affecting [[granulosa cell]]s.<ref name="Colorado">{{cite web|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/lhfsh.html|archive-url=https://web.archive.org/web/20040302135139/http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/lhfsh.html|url-status=dead|archive-date=2 March 2004|title=Gonadotropins: Luteinizing and Follicle Stimulating Hormones| vauthors = Bowen R |date=13 May 2004|publisher=Colorado State University|access-date=12 March 2012}}</ref> With the rise in [[oestrogen|estrogen]]s, 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 [[oestrogen|estrogen]]s. 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]].<ref>{{cite journal | vauthors = Mahesh VB | title = Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 302 | issue = 1 | pages = E4–E18 | date = January 2012 | pmid = 22028409 | pmc = 3328092 | doi = 10.1152/ajpendo.00488.2011 }}</ref> 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.<ref>{{cite journal | vauthors = Micevych P, Sinchak K | title = The Neurosteroid Progesterone Underlies Estrogen Positive Feedback of the LH Surge | journal = Frontiers in Endocrinology | volume = 2 | pages = 90 | date = 2 December 2011 | pmid = 22654832 | pmc = 3356049 | doi = 10.3389/fendo.2011.00090 | doi-access = free }}</ref> 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 (human embryo)|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 ([[oestrogen|estrogen]]s 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. [[gamma-Aminobutyric acid|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.<ref>{{cite book | vauthors = Norris DO, Carr JA |date=2013 |title=Vertebrate Endocrinology |url=https://books.google.com/books?id=F_NaW1ZcSSAC |publisher=Academic Press |page=126 |isbn=978-0-12-396465-6 }}</ref>

===Effects in males===
LH acts upon the [[Leydig cells]] of the [[testis]] and is regulated by  [[GnRH|gonadotropin-releasing hormone]] (GnRH).<ref name="Nedresky_2022">{{cite book | vauthors = Nedresky D, Singh G | chapter = Physiology, Luteinizing Hormone | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | date =  September 2022 | pmid = 30969514 | doi = | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK539692/ }}</ref> The Leydig cells produce [[testosterone]] under the control of LH. LH 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.<ref>{{cite journal | vauthors = Zirkin BR, Papadopoulos V | title = Leydig cells: formation, function, and regulation | journal = Biology of Reproduction | volume = 99 | issue = 1 | pages = 101–111 | date = July 2018 | pmid = 29566165 | pmc = 6044347 | doi = 10.1093/biolre/ioy059 }}</ref> Pregnenolone is then converted to dehydroepiandrosterone (DHEA).<ref>{{cite journal | vauthors = Akhtar MK, Kelly SL, Kaderbhai MA | title = Cytochrome b(5) modulation of 17{alpha} hydroxylase and 17-20 lyase (CYP17) activities in steroidogenesis | journal = The Journal of Endocrinology | volume = 187 | issue = 2 | pages = 267–274 | date = November 2005 | pmid = 16293774 | doi = 10.1677/joe.1.06375 | doi-access = free }}</ref> DHEA is then converted to androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD)<ref>{{cite journal | vauthors = Liu L, Kang J, Ding X, Chen D, Zhou Y, Ma H | title = Dehydroepiandrosterone-Regulated Testosterone Biosynthesis via Activation of the ERK1/2 Signaling Pathway in Primary Rat Leydig Cells | journal = Cellular Physiology and Biochemistry | volume = 36 | issue = 5 | pages = 1778–1792 | date = 2015 | pmid = 26184424 | doi = 10.1159/000430150 | s2cid = 13816368 | doi-access = free }}</ref> 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 LH signals the release of testosterone,<ref>{{cite journal | vauthors = Oduwole OO, Peltoketo H, Huhtaniemi IT | title = Role of Follicle-Stimulating Hormone in Spermatogenesis | journal = Frontiers in Endocrinology | volume = 9 | pages = 763 | year = 2018 | pmid = 30619093 | pmc = 6302021 | doi = 10.3389/fendo.2018.00763 | doi-access = free }}</ref> 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  [[GnRH|gonadotropin-releasing hormone]]. When bloodstream testosterone levels are low, the pituitary gland is stimulated to release LH.<ref name="Nedresky_2022" /> 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.<ref>{{cite journal | vauthors = Tilbrook AJ, Clarke IJ | title = Negative feedback regulation of the secretion and actions of gonadotropin-releasing hormone in males | journal = Biology of Reproduction | volume = 64 | issue = 3 | pages = 735–742 | date = March 2001 | pmid = 11207186 | doi = 10.1095/biolreprod64.3.735 }}</ref> 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)<ref>{{cite journal | vauthors = Ubuka T, Son YL, Tobari Y, Narihiro M, Bentley GE, Kriegsfeld LJ, Tsutsui K | title = Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor | journal = Frontiers in Endocrinology | volume = 5 | pages = 8 | year = 2014 | pmid = 24478760 | pmc = 3902780 | doi = 10.3389/fendo.2014.00008 | doi-access = free }}</ref> 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.<ref name="Pitteloud">{{cite journal | vauthors = Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF, Hayes FJ | title = 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 | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 93 | issue = 3 | pages = 784–791 | date = March 2008 | pmid = 18073301 | pmc = 2266963 | doi = 10.1210/jc.2007-2156 }}</ref>

Changes in LH and testosterone blood levels and pulse secretions are induced by changes in [[sexual arousal]] in human males.<ref name="Stoleru">{{cite journal | vauthors = Stoléru SG, Ennaji A, Cournot A, Spira A | title = LH pulsatile secretion and testosterone blood levels are influenced by sexual arousal in human males | journal = Psychoneuroendocrinology | volume = 18 | issue = 3 | pages = 205–218 | year = 1993 | pmid = 8516424 | doi = 10.1016/0306-4530(93)90005-6 | s2cid = 23595343 }}</ref>

=== Effects in the brain ===
Luteinizing hormone receptors are located in areas of the brain associated with [[cognitive function]].<ref name="Blair_2015" /> The role of LH role in the [[central nervous system]] (CNS) may be of relevance to understanding and treating post-menopausal cognitive decline.<ref>{{Cite journal | vauthors = Than S, Moran C, Beare R, Vincent A, Lane E, Collyer TA, Callisaya ML, Srikanth V |date=2023 |title=Cognitive trajectories during the menopausal transition |journal=Frontiers in Dementia |volume=2 |doi=10.3389/frdem.2023.1098693 |issn=2813-3919 | doi-access = free |pmid=39081973 |pmc=11285668 }}</ref>

Some research has observed an inverse relationship between circulating LH and CNS LH levels.<ref>{{cite journal | vauthors = Bhatta S, Blair JA, Casadesus G | title = Luteinizing Hormone Involvement in Aging Female Cognition: Not All Is Estrogen Loss | journal = Frontiers in Endocrinology | volume = 9 | pages = 544 | date = 24 September 2018 | pmid = 30319538 | pmc = 6165885 | doi = 10.3389/fendo.2018.00544 | doi-access = free }}</ref> After ovariectomy (a procedure used to mimic menopause) in female mice, circulating LH levels surge while CNS levels of LH fall.<ref name="Blair_2015">{{cite journal | vauthors = Blair JA, Bhatta S, McGee H, Casadesus G | title = Luteinizing hormone: Evidence for direct action in the CNS | journal = Hormones and Behavior | volume = 76 | pages = 57–62 | date = November 2015 | pmid = 26172857 | pmc = 4741372 | doi = 10.1016/j.yhbeh.2015.06.020 }}</ref> Treatments that lower circulating LH restore LH levels in the CNS.<ref name="Blair_2015" />