Relaxin
Encyclopedia
Relaxin is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 first described in 1926 by Frederick Hisaw.

The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 (RNL1), 2 (RNL2) and 3 (RNL3), and the insulin-like (INSL) peptides, INSL3
INSL3
Insulin-like 3 is a protein that in humans is encoded by the INSL3 gene.-Further reading:...

, INSL4
INSL4
Early placenta insulin-like peptide is a protein that in humans is encoded by the INSL4 gene.-Further reading:...

, INSL5
INSL5
Insulin-like peptide INSL5 is a protein that in humans is encoded by the INSL5 gene.-Further reading:...

 and INSL6. The functions of relaxin-3, INSL4, INSL5, INSL6 remain uncharacterised.

Synthesis

In the female, it is produced by the corpus luteum
Corpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...

 of the 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...

, the 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...

 and, during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

, also by the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

, chorion
Chorion
The chorion is one of the membranes that exist during pregnancy between the developing fetus and mother. It is formed by extraembryonic mesoderm and the two layers of trophoblast and surrounds the embryo and other membranes...

, and decidua
Decidua
Decidua is the term for the uterine lining during a pregnancy, which forms the maternal part of the placenta. It is formed under the influence of progesterone and forms highly-characteristic cells.-Etymology:...

.

In the male, it is produced in the prostate and is present in human semen.

Structure

Structurally, relaxin is a heterodimer of two peptide chains of 24 and 29 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s linked by disulfide
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....

 bridges, and it appears related to insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

.

Relaxin is produced from its prohormone
Prohormone
A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. The primary function of a prohormone is to enhance the strength of the hormone that already occurs in the...

, “prorelaxin”, by splitting off one additional peptide chain.

In humans

In males, relaxin enhances motility of sperm in semen.
In females relaxin is produced mainly by the corpus luteum, in both pregnant and nonpregnant females; it rises to a peak within approximately 14 days of ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...

, and then declines in the absence of pregnancy, resulting in menstruation
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...

. During the first trimester of pregnancy, levels rise and additional relaxin is produced by the decidua.

Relaxin's role or necessity in human pregnancy remains under investigation, as in humans its peak is reached during the 14 weeks of the first trimester and at delivery. It is believed to soften the pubic symphysis
Pubic symphysis
The pubic symphysis or symphysis pubis is the midline cartilaginous joint uniting the superior rami of the left and right pubic bones. It is located anterior to the urinary bladder and superior to the external genitalia; for females it is above the vulva and for males it is above the penis...

.

In other animals

In animals, relaxin widens the pubic bone and facilitates labor
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

; it also softens the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

 (cervical ripening), and relaxes the uterine musculature. Thus, for a long time, relaxin was looked at as a pregnancy hormone. However, its significance may reach much further. Relaxin affects collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...

 metabolism, inhibiting collagen synthesis and enhancing its breakdown by increasing matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....

s. It also enhances angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

 and is a potent renal vasodilator.

Receptors

Relaxin interacts with the relaxin receptor
Relaxin receptor
The relaxin receptors are a subclass of four closely related G protein-coupled receptors that bind relaxin peptide hormones.Below is list of human relaxin receptors, their endogenous peptide hormones, and what down stream enzymes are activated or inhibited by the receptor....

 LGR7 (RXFP1) and LGR8 (RXFP2), which belong to the 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...

 superfamily . They contain a heptahelical transmembrane domain
Transmembrane helix
Transmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can fold independently from the rest of the protein, similar to domains of water-soluble proteins...

 and a large glycosylated ectodomain, distantly related to the receptors for the glycoproteohormones, such as the LH-receptor or FSH-receptor
FSH-receptor
The follicle-stimulating hormone receptor or FSH-receptor is a transmembrane receptor that interacts with the follicle-stimulating hormone and represents a G protein-coupled receptor . Its activation is necessary for the hormonal functioning of FSH...

.

Relaxin receptors have been found in the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

, the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...

, and central and autonomous nervous system.

Disorders

Specific disorders related to relaxin have not been described, yet a link to scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...

 and fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...

has been suggested.
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