For other uses of the term FSH, see FSH (disambiguation).
| glycoprotein hormones, alpha polypeptide |
| Identifiers |
| Symbol |
CGA |
| Entrez |
1081 |
| HUGO |
1885 |
| OMIM |
118850 |
| RefSeq |
NM_000735 |
| UniProt |
P01215 |
| Other data |
| Locus |
Chr. 6 q14-q21 |
| follicle stimulating hormone, beta polypeptide |
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| Follicle-stimulating hormone |
| Identifiers |
| Symbol |
FSHB |
| Entrez |
2488 |
| HUGO |
3964 |
| OMIM |
136530 |
| RefSeq |
NM_000510 |
| UniProt |
P01225 |
| Other data |
| Locus |
Chr. 11 p13 |
Follicle-stimulating hormone (FSH) is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland.[1] FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) act synergistically in reproduction. Specifically, an increase in FSH secretion by the anterior pituitary causes ovulation.
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Contents
- 1 Structure
- 2 Genes
- 3 Activity
- 3.1 Effects in females
- 3.2 Effects in males
- 4 Measurement
- 5 Disease states
- 5.1 High FSH levels
- 5.2 Low FSH levels
- 6 Availability
- 7 Potential role in vascularization of solid tumors
- 8 References
- 9 External links
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Structure
FSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached to it; two of these make the full, functional protein. Its structure is similar to those of LH, TSH, and hCG. The protein dimer contains 2 polypeptide units, labeled alpha and beta subunits. The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids. The beta subunits vary. FSH has a beta subunit of 111amino acids (FSH β), which confers its specific biologic action and is responsible for interaction with the FSH-receptor. The sugar part of the hormone is composed of fucose, galactose, mannose, galactosamine, glucosamine, and sialic acid, the latter being critical for its biologic half-life. The half-life of FSH is 3–4 hours.
The 92-amino-acid-long FSH alpha subunit in humans has the following sequence:
NH2 – Ala – Pro – Asp – Val – Gln – Asp – Cys – Pro – Glu – Cys – Thr – Leu – Gln – Glu – Asn – Pro – Phe – Phe – Ser – Gln – Pro – Gly – Ala – Pro – Ile – Leu – Gln – Cys – Met – Gly – Cys – Cys – Phe – Ser – Arg – Ala – Tyr – Pro – Thr – Pro – Leu – Arg – Ser† – Lys – Lys – Thr – Met – Leu – Val – Gln – Lys – Asn – Val – Thr – Ser – Glu – Ser – Thr – Cys – Cys – Val – Ala – Lys – Ser – Tyr – Asn – Arg – Val – Thr – Val – Met – Gly – Gly – Phe – Lys – Val – Glu – Asn – His – Thr – Ala – Cys – His – Cys – Ser – Thr – Cys – Tyr – Tyr – His – Lys – Ser – OH
- Note: The carbohydrate moiety is linked to the asparagine at positions 52 and 78.
The 111-amino-acid-long FSH beta subunit in humans has the following sequence:
NH2 – Asn – Ser – Cys – Glu – Leu – Thr – Asn – Ile – Thr – Ile – Ala – Ile – Glu – Lys – Glu – Glu – Cys – Arg – Phe – Cys – Ile – Ser – Ile – Asn – Thr – Thr – Trp – Cys – Ala – Gly – Tyr – Cys – Tyr – Thr – Arg – Asp – Leu – Val – Tyr – Lys – Asp – Pro – Ala – Arg – Pro – Lys – Ile – Gln – Lys – Thr – Cys – Thr – Phe – Lys – Glu – Leu – Val – Tyr – Glu – Thr – Val – Arg – Val – Pro – Gly – Cys – Ala – His – His – Ala – Asp – Ser – Leu – Tyr – Thr – Tyr – Pro – Val – Ala – Thr – Gln – Cys – His – Cys – Gly – Lys – Cys – Asp – Ser – Asp – Ser – Thr – Asp – Cys – Thr – Val – Arg – Gly – Leu – Gly – Pro – Ser – Tyr – Cys – Ser – Phe – Gly – Glu – Met – Lys – Glu – OH
- Note: The carbohydrate moiety is linked to the asparagine at positions 7 and 24.
Genes
The gene for the alpha subunit is located on chromosome 6p21.1-23. It is expressed in different cell types. The gene for the FSH beta subunit is located on chromosome 11p13, and is expressed in gonadotropes of the pituitary cells, controlled by GnRH, inhibited by inhibin, and enhanced by activin.
Activity
FSH regulates the development, growth, pubertal maturation, and reproductive processes of the human body.
- In both males and females, FSH stimulates the maturation of germ cells.
- In males, FSH induces Sertoli cells to secrete inhibin and stimulates the formation of sertoli-sertoli tight junctions (zonula occludens).
- In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the concomitant rise in inhibin B, FSH levels then decline in the late follicular phase. This seems to be critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal phase, there is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle.
Like its partner LH, FSH release at the pituitary gland is controlled by pulses of gonadotropin-releasing hormone (GnRH). Those pulses, in turn, are subject to the oestrogen feed-back from the gonads.
Reference ranges for the blood content of follicle-stimulating hormone levels during the menstrual cycle.[2]
- 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.
Effects in females
FSH stimulates the growth and recruitment of immature ovarian follicles in the ovary. In early (small) antral follicles, FSH is the major survival factor that rescues the small antral follicles (2–5 mm in diameter for humans) from apoptosis (programmed death of the somatic cells of the follicle and oocyte). In the luteal-follicle phase transition period the serum levels of progesterone and estrogen (primarily estradiol) decrease and no longer suppress the release of FSH, consequently FSH peaks at about day three (day one is the first day of menstrual flow). The cohort of small antral follicles is normally sufficiently in number to produce enough Inhibin B to lower FSH serum levels.
In addition, there is evidence that gonadotrophin surge-attenuating factor produced by small follicles during the first half of the follicle phase also exerts a negative feedback on pulsatile luteinizing hormone (LH) secretion amplitude, thus allowing a more favorable environment for follicle growth and preventing premature luteinization.[3]
(As a woman nears perimenopause, the number of small antral follicles recruited in each cycle diminishes and consequently insufficient Inhibin B is produced to fully lower FSH and the serum level of FSH begins to rise. Eventually the FSH level becomes so high that downregulation of FSH receptors occurs and by menopause any remaining small secondary follicles no longer have FSH receptors.)
When the follicle matures and reaches 8–10 mm in diameter it starts to secrete significant amounts of estradiol. Normally in humans only one follicle becomes dominant and survives to grow to 18–30 mm in size and ovulate, the remaining follicles in the cohort undergo atresia. The sharp increase in estradiol production by the dominant follicle (possibly along with a decrease in gonadotrophin surge-attenuating factor) cause a positive effect on the hypothalamus and pituitary and rapid GnRH pulses occur and an LH surge results.
The increase in serum estradiol levels cause a decrease in FSH production by inhibiting GnRH production in the hypothalamus.[4]
The decrease in serum FSH level causes the smaller follicles in the current cohort to undergo atresia as they lack sufficient sensitivity to FSH to survive. Occasionally two follicles reach the 10 mm stage at the same time by chance and as both are equally sensitive to FSH both survive and grow in the low FSH environment and thus two ovulations can occur in one cycle possibly leading to non identical (dizygotic) twins.
Effects in males
FSH stimulates primary spermatocytes to undergo the first division of meiosis, to form secondary spermatocytes.
FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes by binding to FSH receptors on their basolateral membranes,[5] and is critical for the initiation of spermatogenesis.
Measurement
Follicle stimulating hormone is typically measured in the early follicular phase of the menstrual cycle, typically day three to five, counted from last menstruation. At this time, the levels of estradiol (E2) and progesterone are at the lowest point of the menstrual cycle. FSH levels in this time is often called basal FSH levels, to distinguish from the increased levels when approaching ovulation.
Disease states
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This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (September 2010) |
FSH levels are normally low during childhood and, in females, high after menopause.
High FSH levels
The most common reason for high serum FSH concentration is in a female who is undergoing or has recently undergone menopause. High levels of Follicle-Stimulating Hormone indicate that the normal restricting feedback from the gonad is absent, leading to an unrestricted pituitary FSH production.
If high FSH levels occur during the reproductive years, it is abnormal. Conditions with high FSH levels include:
- Premature menopause also known as Premature Ovarian Failure
- Poor ovarian reserve also known as Premature Ovarian Aging
- Gonadal dysgenesis, Turner syndrome
- Castration
- Swyer syndrome
- Certain forms of CAH
- Testicular failure.
- Klinefelter syndrome
Most of these conditions are associated with subfertility and/or infertility. Therefore high FSH levels are an indication of subfertility and/or infertility.
Low FSH levels
Diminished secretion of FSH can result in failure of gonadal function (hypogonadism). This condition is typically manifested in males as failure in production of normal numbers of sperm. In females, cessation of reproductive cycles is commonly observed. Conditions with very low FSH secretions are:
- Polycystic Ovarian Syndrome
- Polycystic Ovarian Syndrome + Obesity + Hirsutism + Infertility
- Kallmann syndrome
- Hypothalamic suppression
- Hypopituitarism
- Hyperprolactinemia
- Gonadotropin deficiency
- Gonadal suppression therapy
- GnRH antagonist
- GnRH agonist (downregulation).
Availability
FSH is available mixed with LH activity in various menotropins including more purified forms of urinary gonadotropins such as Menopur, as well as without LH activity as recombinant FSH (Gonal F, Follistim, Follitropin alpha). It is used commonly in infertility therapy to stimulate follicular development, notably in IVF therapy, as well as with interuterine insemination (IUI). (See Gonadotropin Preparations.)
Potential role in vascularization of solid tumors
Elevated FSH receptor levels have been detected in the endothelia of tumor vasculature in a very wide range of solid tumors. FSH binding is thought to upregulate neovascularization via at least two mechanisms - one in the VEGF pathway, and the other VEGF independent - related to the development of umbilical vasculature when physiological. This presents possible use of FSH and FSH-receptor antagonists as an anti tumor angiogenesis therapy (cf. avastin for current anti-VEGF approaches).[6]
References
- ^ "Follicle-Stimulating Hormone". http://women.webmd.com/follicle-stimulating-hormone.
- ^ References and further description of values are given in image page in Wikimedia Commons at Commons:File:Follicle-stimulating hormone (FSH) during menstrual cycle.png.
- ^ Fowler PA, Sorsa-Leslie T, Harris W, Mason HD (December 2003). "Ovarian gonadotrophin surge-attenuating factor (GnSAF): where are we after 20 years of research?". Reproduction 126 (6): 689–99. doi:10.1530/rep.0.1260689. PMID 14748688.
- ^ Dickerson LM, Shrader SP, Diaz VA (2008). "Chapter 8: Contraception". In Wells BG, DiPiro JT, Talbert RL, Yee GC, Matzke GR. Pharmacotherapy: a pathophysiologic approach. McGraw-Hill Medical. pp. 1313–28. ISBN 0-07-147899-X.
- ^ Boulpaep EL, Boron WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. pp. 1125. ISBN 1-4160-2328-3.
- ^ Radu A, Pichon C, Camparo P, Antoine M, Allory Y, Couvelard A, Fromont G, Hai MT, Ghinea N (October 2010). "Expression of follicle-stimulating hormone receptor in tumor blood vessels". N. Engl. J. Med. 363 (17): 1621–30. doi:10.1056/NEJMoa1001283. PMID 20961245.
External links
- Day 3 FSH levels From the Infertility Blog by Dr. Fred Licciardi
- High FSH: an excuse to send patients away From the Infertility Blog by Dr. Fred Licciardi
- FSH and Estradiol
- Causes & Symptoms of High FSH
- Information on high FSH compiled by a woman with high FSH
- High FSH Levels background information
- Getting Pregnant with High FSH by Julia Indichova, author of Inconceivable (Doubleday 2001) and The Fertile Female (Adell Press 2007)
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Endocrine system: hormones (Peptide hormones · Steroid hormones)
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Endocrine
glands |
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Hypothalamic-
pituitary
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Hypothalamus
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GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone
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Posterior pituitary
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Vasopressin · Oxytocin
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Anterior pituitary
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α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH
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Adrenal axis
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Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine
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Thyroid axis
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Thyroid: thyroid hormone (T3 and T4) · calcitonin
Parathyroid: PTH
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Gonadal axis
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Testis: testosterone · AMH · inhibin
Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)
Placenta: hCG · HPL · estrogen · progesterone
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Islet-Acinar
Axis
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Pancreas: glucagon · insulin · amylin · somatostatin · pancreatic polypeptide
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Pineal gland
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Pineal gland: melatonin
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Non-end.
glands |
Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin
Digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · Incretins (GIP, GLP-1) · secretin · motilin · VIP · Ileum: enteroglucagon · peptide YY · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Adipose tissue: leptin · adiponectin · resistin
Skeleton: Osteocalcin
Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin
Heart: Natriuretic peptide (ANP, BNP)
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noco (d)/cong/tumr, sysi/epon
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proc, drug (A10/H1/H2/H3/H5)
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Assisted reproductive technology
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| Infertility |
- Female
- Male
- Fertility clinic
- Fertility tourism
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| Fertility medication |
- GnRH agonists
- Estrogen antagonists
- Clomifene
- Aromatase inhibitor
- Gonadotropins
- hCG
- FSH
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In vitro fertilisation (IVF)
and expansions |
- Ovarian hyperstimulation
- Transvaginal ovum retrieval
- Embryo transfer
- Assisted zona hatching
- Intracytoplasmic sperm injection
- Autologous endometrial coculture
- zygote intrafallopian transfer
- Cytoplasmic transfer
- Egg donation
- gestational carrier
- Preimplantation genetic diagnosis
- In vitro maturation
- Oocyte selection
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| Other methods |
- Gamete intrafallopian transfer
- Sex selection
- Artificial insemination
- Surrogacy
- Reproductive surgery
- Semen collection
- Cryopreservation
- oocyte
- semen
- ovarian tissue
- embryos
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| Donation |
- Sperm
- Egg
- Embryo
- Sperm bank
- Donor registration
- Donor Sibling Registry
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| Ethics |
- Religious response to ART
- Accidental incest
- Three-parent babies
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| In fiction |
- See subsections in e.g. surrogacy and sperm donation
- reproduction and pregnancy in speculative fiction
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noco/cong/npls, sysi/epon
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proc/asst, drug (G1/G2B/G3CD)
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