Gonadotropins are
glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s secreted by
gonadotropic cell
1. Introduction
Gonadotropic cells (also known as gonadotropes, gonadotrophs, delta cells, or delta basophils) are endocrine cells in the anterior pituitary that produce gonadotropins. More specifically, gonadotrophs produce and secrete glyc ...
s of the
anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
of
vertebrate
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
s.
They are central to the complex
endocrine system
The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant Organ (biology), organs. In vertebrat ...
that regulates normal
growth,
sexual development
Puberty is the process of physical changes through which a child's Human body, body matures into an adult body capable of sexual reproduction. It is initiated by hormone, hormonal signals from the Human brain, brain to the gonads: the ovary ...
, and
reproductive function.
The hormone family includes the
mammal
A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
ian hormones
follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH) and
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH), the
placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
l/
chorion
The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It is also present around the embryo of other animals, like insects and molluscs.
Structure
In humans and other therian mammals, the cho ...
ic gonadotropins,
human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
(hCG) and
equine chorionic gonadotropin (eCG),
as well as at least two forms of
fish
A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...
gonadotropins. LH and FSH are secreted by the anterior
pituitary gland
The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
, while hCG and eCG are secreted by the placenta in
pregnant
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
women and
mare
A mare is an adult female horse or other equidae, equine. In most cases, a mare is a female horse over the age of three, and a filly is a female horse three and younger. In Thoroughbred horse racing, a mare is defined as a female horse more th ...
s, respectively.
The gonadotropins act on the
gonad
A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...
s, controlling
gamete
A gamete ( ) is a Ploidy#Haploid and monoploid, haploid cell that fuses with another haploid cell during fertilization in organisms that Sexual reproduction, reproduce sexually. Gametes are an organism's reproductive cells, also referred to as s ...
and
sex hormone
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
production.
Gonadotropin is sometimes abbreviated ''Gn''. The alternative spelling ''gonadotrophin'' which inaccurately implies a nourishing mechanism is also used.
There are various
preparations of gonadotropins for
therapeutic
A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx.
As a rule, each therapy has indications an ...
use, mainly as
fertility medication
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. There are also
fad diet
A fad diet is a diet that is popular, generally only for a short time, similar to fads in fashion, without being a standard scientific dietary recommendation, and often making unreasonable claims for fast weight loss or health improvements; ...
or
quack preparations, which are illegal in various countries.
Natural types and subunit structure
The two principal gonadotropins in vertebrates are
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH) and
follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH), although primates produce a third gonadotropin called
chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
(CG). LH and FSH are heterodimers consisting of two
peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
chains,
an alpha chain and a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity for
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
interactions. These subunits are heavily modified by
glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
.
The alpha subunit is common to each protein dimer (well conserved within species, but differing between them),
and a unique beta subunit confers biological specificity.
The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds,
as shown in the following schematic representation.
+---------------------------+
+----------+, +-------------, --+
, , , , , ,
, , , ,
+------, -----------------+ ,
, ,
+----------------------------+
'C': conserved cysteine involved in a disulphide bond.
Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated.
Another human gonadotropin is
human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantat ...
(hCG), produced by the
placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
during
pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
.
Mechanism
Gonadotropin receptors are embedded in the surface of the target
cell membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
s and coupled to the
G-protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their ...
system. Signals triggered by binding to the receptor are relayed within the cells by the
cyclic AMP
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triph ...
second messenger system.
Gonadotropins are released under the control of
gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...
(GnRH) from the arcuate nucleus and preoptic area of the
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. The
gonad
A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...
s —
testes
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone.
The ...
and
ovaries
The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
— are the primary target organs for LH and FSH. The gonadotropins affect multiple cell types and elicit multiple responses from the target organs. As a simplified generalization, LH stimulates the
Leydig cells of the testes and the
theca cell
The theca folliculi comprise a layer of the ovarian follicles. They appear as the follicles become secondary follicles.
The theca are divided into two layers, the theca interna and the theca externa.
Theca cells are a group of endocrine cel ...
s of the ovaries to produce
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
(and indirectly
estradiol
Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
), whereas FSH stimulates the spermatogenic tissue of the
testes
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone.
The ...
and the
granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the Folliculogenesis#Primordial, primo ...
s of
ovarian follicle
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. In humans, women have approximately 200,000 to 300,000 follicles at the time of puberty, ea ...
s, as well as stimulating production of
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
by the ovaries.
Although gonadotropins are secreted in a
pulsatile manner (as a result of pulsatile GnRH release), unlike the case of GnRH and
GnRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...
s, constant/non-pulsatile activation of the gonadotropin receptors by the gonadotropins does not produce functional inhibition. This can be seen during the first 7–10 weeks of pregnancy, where constantly high and progressively-increasing levels of hCG circulate and mediate production of estrogen and progesterone by the
corpus luteum
The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
until the
placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
takes over the production of these hormones.
Diseases
Gonadotropin deficiency due to
pituitary
The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus control much of th ...
disease results in
hypogonadism
Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...
, which can lead to
infertility
In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
. Treatment includes administered gonadotropins, which, therefore, work as
fertility medication
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. Such can either be produced by extraction and purification from urine or be produced by
recombinant DNA
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
.
Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood.
LH insensitivity, which results in
Leydig cell hypoplasia in males, and
FSH insensitivity, are conditions of insensitivity to LH and FSH, respectively, caused by
loss-of-function mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis ...
s in their respective signaling receptors. Another closely related condition to these is
GnRH insensitivity.
Pharmaceutical preparations
There are various
preparations of gonadotropins for
therapeutic
A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx.
As a rule, each therapy has indications an ...
use, mainly as
fertility medication
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. For example, the so-called
menotropins (also called ''human menopausal gonadotropins'') consist of LH and FSH extracted from the
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
of
menopausal women.
There are also
recombinant variants. Besides the aforementioned legitimate
pharmaceutical drug
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
s, there are
fad diet
A fad diet is a diet that is popular, generally only for a short time, similar to fads in fashion, without being a standard scientific dietary recommendation, and often making unreasonable claims for fast weight loss or health improvements; ...
or
quack preparations, which are illegal in various countries.
See also
*
Antigonadotropin
An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituit ...
*
Gonadotropin surge-attenuating factor
References
External links
*
10th International Symposium on GnRH
{{Authority control
Peptide hormones
Hormones of the hypothalamus-pituitary-gonad axis
Gonadotropin-releasing hormone and gonadotropins
Animal reproductive system
Sex hormones