Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintaining

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

(i.e., ''progestational''), although they are also present at other phases of the

estrous The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous p ...

and menstrual cycles. The progestogens are one of three types of sex hormones, the others being

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...

s like estradiol and androgens/ anabolic steroids like testosterone. In addition, they are one of the five major classes of steroid hormones, the others being the androgens, estrogens,

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verte ...

s, and mineralocorticoids, as well as the neurosteroids. All endogenous progestogens are characterized by their basic 21-carbon skeleton, called a pregnane skeleton (C21). In similar manner, the estrogens possess an estrane skeleton (C18), and androgens, an androstane skeleton (C19). The terms ''progesterone'', ''progestogen'', and ''progestin'' are mistakenly used interchangeably both in the scientific literature and in clinical settings. '' Progestins'' are ''

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

progestogens'' and are used in medicine. Major examples of progestins include the 17α-hydroxyprogesterone derivative medroxyprogesterone acetate and the 19-nortestosterone derivative

norethisterone Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in ...

. The progestins are structural analogues of progesterone and have progestogenic activity similarly, but differ from progesterone in their pharmacological properties in various ways. In addition to their roles as natural hormones, progestogens are used as

medication A medication (also called medicament, medicine, pharmaceutical drug, 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 medical field an ...

s, for instance in menopausal hormone therapy and

transgender hormone therapy Transgender hormone therapy, also called hormone replacement therapy (HRT) or gender-affirming hormone therapy (GAHT), is a form of hormone therapy in which sex hormones and other hormonal medications are administered to transgender or gender ...

for transgender women; for information on progestogens as medications, see the progesterone (medication) and progestogen (medication) articles.

Types and examples

The most important progestogen in the body is progesterone (P4). Other endogenous progestogens, with varying degrees of progestogenic activity, include 16α-hydroxyprogesterone (16α-OHP), 17α-hydroxyprogesterone (17α-OHP) (very weak),

20α-dihydroprogesterone 20α-Dihydroprogesterone (20α-DHP), also known as 20α-hydroxyprogesterone (20α-OHP), is a naturally occurring, endogenous progestogen. It is a metabolite of progesterone, formed by the 20α-hydroxysteroid dehydrogenases (20α-HSDs) AKR1C1, AKR1 ...

(20α-DHP), 20β-dihydroprogesterone (20β-DHP), 5α-dihydroprogesterone (5α-DHP), 5β-dihydroprogesterone (5β-DHP) (very weak), 3β-dihydroprogesterone (3β-DHP),

11-deoxycorticosterone 11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone ( INN), deoxycortone, and cortexone, is a steroid hormone produced by the adrenal gland that possesses mineralocorticoi ...

(DOC), and

5α-dihydrodeoxycorticosterone 5α-Dihydrodeoxycorticosterone (abbreviated as DHDOC), also known as 21-hydroxy-5α-pregnan-20-one, is an endogenous progestogen and neurosteroid. It is synthesized from the adrenal hormone deoxycorticosterone (DOC) by the enzyme 5α-reductase t ...

(5α-DHDOC). They are all

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s of progesterone, lying downstream of progesterone in terms of biosynthesis.

Biological function

The major tissues affected by progestogens include the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hy ...

, cervix,

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and s ...

s, testes, and

brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...

. The main biological role of progestogens in the body is in the female reproductive system, and the male reproductive system, with involvement in regulation of the menstrual cycle, maintenance of

, and preparation of the mammary glands for

lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The pr ...

and

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

following parturition in women; in men progesterone affects spermiogenesis, sperm capacitation, and testosterone synthesis. Progestogens also have effects in other parts of the body. Unlike

s, progestogens have little or no role in feminization.

Biochemistry

Biosynthesis

Progesterone is produced from cholesterol with pregnenolone as a metabolic intermediate. In the first step in the

steroidogenic pathway A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

, cholesterol is converted into pregnenolone, which serves as the precursor to the progestogens progesterone and 17α-hydroxyprogesterone. These progestogens, along with another steroid, 17α-hydroxypregnenolone, are the precursors of all other endogenous steroids, including the androgens, estrogens, glucocorticoids, mineralocorticoids, and neurosteroids. Thus, many tissues producing steroids, including the adrenal glands, testes, and ovaries, produce progestogens. In some tissues, the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

s required for the final product are not all located in a single cell. For example, in ovarian follicles, cholesterol is converted to

androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehy ...

, an androgen, in the theca cells, which is then further converted into estrogen in the granulosa cells. Fetal adrenal glands also produce pregnenolone in some species, which is converted into progesterone and estrogens by the placenta (see below). In the human, the fetal adrenals produce dehydroepiandrosterone (DHEA) via the pregnenolone pathway.

Ovarian production

Progesterone is the major progestogen produced by the corpus luteum of the ovary in all mammalian species. Luteal cells possess the necessary enzymes to convert cholesterol to pregnenolone, which is subsequently converted into progesterone. Progesterone is highest in the diestrus phase of the estrous cycle.

Placental production

The role of the placenta in progestogen production varies by species. In the sheep, horse, and human, the

placenta The placenta is a temporary embryonic and later fetal organ (anatomy), organ that begins embryonic development, developing from the blastocyst shortly after implantation (embryology), implantation. It plays critical roles in facilitating nutrien ...

takes over the majority of progestogen production, whereas in other species the corpus luteum remains the primary source of progestogens. In the sheep and human, progesterone is the major placental progestogen. The equine placenta produces a variety of progestogens, primarily 5α-dihydroprogesterone and 5α,20α-tetrahydroprogesterone, beginning on day 60. A complete luteo-placental shift occurs by day 120–150.

Chemistry

The endogenous progestogens are naturally occurring pregnane

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

s with

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

and/or hydroxyl groups at the C3 and C20 positions.

Medical use

Progestogens, including both progesterone and progestins, are used medically in hormonal birth control, hormone therapy, to treat gynecological disorders, to suppress sex hormone levels for various purposes, and for other indications.

References

External links

*
The Nomenclature of Steroids

{{Progesterone receptor modulators Hormones of the hypothalamus-pituitary-gonad axis Hormones of the hypothalamic-pituitary-prolactin axis Hormones of the pregnant female Prolactin releasers Sex hormones