Gonadotropin-releasing hormone receptor
Encyclopedia
The gonadotropin-releasing hormone receptor (GNRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocyte
s, breast
, ovary
, and prostate
.
This receptor is a 60 kDa
G protein-coupled receptor
and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus
. Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary.
Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancer
s.
(PtdIns)-calcium
second messenger system. Activation of GNRHR ultimately causes the release of follicle stimulating hormone (FSH) and luteinizing hormone
(LH).
and GNRHR2
).
Alternative splicing of the GNRHR gene, GNRHR, results in multiple transcript
variants encoding different isoforms. More than 18 transcription
initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for GNRHR.
.
Normal puberty
begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner or much later or in many cases never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide. Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.
The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is the gonadotropin-releasing hormone (GnRH). GnRH is produced in the hypothalamus but gets secreted and acts upon receptors (GnRH-R
) on the anterior pituitary
to exert its effects on reproductive maturation
.
Understanding how GnRH-R functions has been key to developing clinical strategies to treat reproductive-related disorders.
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
, ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, and prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
.
This receptor is a 60 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary.
Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s.
Function
Following binding of Gonadotropin releasing hormone (GNRH), GNRHR associates with G-proteins that activate a phosphatidylinositolPhosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
(PtdIns)-calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
second messenger system. Activation of GNRHR ultimately causes the release of follicle stimulating hormone (FSH) and luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH).
Genes
There are two major forms of the GNRHR, each encoded by a separate gene (GNRHRGNRHR
Gonadotropin-releasing hormone receptor is a protein that in humans is encoded by the GNRHR gene.-Further reading:...
and GNRHR2
GNRHR2
Putative gonadotropin-releasing hormone II receptor is a protein that in humans is encoded by the GNRHR2 gene.- Function :The receptor for gonadotropin releasing hormone 2 is encoded by the GnRH2 receptor gene. In non-hominoid primates and non-mammalian vertebrates, GnRHR2 encodes a...
).
Alternative splicing of the GNRHR gene, GNRHR, results in multiple transcript
Transcript
Transcript may refer to:* Transcript , a copy of a student's permanent academic record* Transcription , the process of creating an equivalent RNA copy of a sequence of DNA* Transcript , a record of all court proceedings...
variants encoding different isoforms. More than 18 transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for GNRHR.
Regulation
The GNRHR responds to GNRH as well as to synthetic GNRH agonists. Agonists stimulate the receptor, however prolonged exposure leads to a downregulation effect resulting in hypogonadism, an effect that is often medically utilized. GNRH antagonists block the receptor and inhibit gonadotropin release. GNRHRs are further regulated by the presence of sex hormones as well as activin and inhibinActivin and inhibin
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle...
.
Clinical implications
Defects in the GNRHR are a cause of hypogonadotropic hypogonadism (HH).Normal puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner or much later or in many cases never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide. Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.
The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is the gonadotropin-releasing hormone (GnRH). GnRH is produced in the hypothalamus but gets secreted and acts upon receptors (GnRH-R
GNRHR
Gonadotropin-releasing hormone receptor is a protein that in humans is encoded by the GNRHR gene.-Further reading:...
) on the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
to exert its effects on reproductive maturation
Sexual maturity
Sexual maturity is the age or stage when an organism can reproduce. It is sometimes considered synonymous with adulthood, though the two are distinct...
.
Understanding how GnRH-R functions has been key to developing clinical strategies to treat reproductive-related disorders.