Pregnenolone is a steroid

Steroid

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

 hormone involved in the steroidogenesis of progesterone

Progesterone

Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

, mineralocorticoids, glucocorticoids, androgen

Androgen

Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...

s, and estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

s. As such it is a 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...

. Pregnenolone sulfate is a GABA_A antagonist and increases neurogenesis

Neurogenesis

Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...

 in the hippocampus

Hippocampus

The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

.

Chemistry

Like other steroid

Steroid

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

s, pregnenolone consists of four interconnected cyclic hydrocarbons. It contains ketone

Ketone

In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

 and hydroxyl

Hydroxyl

A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 functional groups, two methyl branches, and a double bond at C5, in the B cyclic hydrocarbon ring. Like all steroid hormones, it is hydrophobic. Its esterified version, pregnenolone sulfate, is water-soluble.

Synthesis

Pregnenolone is synthesized from cholesterol

Cholesterol

Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

. This conversion involves hydroxylation at the side-chain at C20 and C22 positions, with cleavage of the side-chain. The enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 performing this task is cytochrome P450scc

P450 scc

Cytochrome P450, family 11, subfamily A, polypeptide 1 , often referred to as P450scc , is a mitochondrial enzyme associated with the conversion of cholesterol to pregnenolone. The gene name is CYP11A1...

, located in the mitochondria, and controlled by pituitary tropic hormones, such as ACTH, FSH

FSH

FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...

, LH

LH

LH, Lh, or lh may stand for:*Laurel and Hardy*Leasehold *Left-handed or left hand*Letterhead, the heading at the top of a sheet of letter paper*lh, a digraph for many languages...

.

Prohormone

Pregnenolone undergoes further steroid metabolism in one of three ways.

• Pregnenolone can be converted to progesterone
  Progesterone
  Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
  
  . The critical enzyme step is two-fold using a 3-beta-hydroxysteroid dehydrogenase and a delta 4-5 isomerase. The latter transfers the double bond
  Double bond
  A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...
  
   from C5 to C4 on the A ring. Progesterone is the entry into the delta-4-pathway, resulting in production of 17-hydroxy progesterone and androstenedione
  Androstenedione
  Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
  
  , precursor to testosterone
  Testosterone
  Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
  
   and estrone
  Estrone
  Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
  
  . Aldosterone
  Aldosterone
  Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
  
   and corticosteroid
  Corticosteroid
  Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
  
  s are also derived from progesterone or its derivatives.

• Pregnenolone can be converted to 17-hydroxy-pregnenolone by the enzyme 17α-hydroxylase (CYP17A1). Using this pathway, termed delta-5 pathway, the next step is conversion to dehydroepiandrosterone
  Dehydroepiandrosterone
  5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
  
   (DHEA) using a desmolase
  Desmolase
  Desmolase is an enzyme that catalyzes the formation or destruction ofcarbon-carbon bonds within a molecule.This enzyme plays a significant role inrespiration and fermentation.Desmolases are a group enzymes involved in steroidogenesis...
  
  . DHEA is the precursor of androstenedione.

• Pregnenolone can be converted to androsta-5,16-dien-3 beta-ol by 16-ene synthetase.

Neurosteroid

Pregnenolone and its sulfate, like dehydroepiandrosterone

Dehydroepiandrosterone

5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....

 and its sulfate and progesterone, belong to the group of neurosteroid

Neuroactive steroid

Neuroactive steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. In addition, these steroids may also exert effects on gene expression via intracellular steroid hormone receptors...

s that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelin

Myelin

Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...

ization. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and memory

Memory

In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....

 functioning.

Pregnenolone sulfate

Pregnenolone sulfate

Pregnenolone sulfate is a derivative of pregnenolone.In some animals, levels can vary depending upon the breeding cycle....

 was shown to activate the Transient Receptor Potential M3

TRPM3

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.TRPM3 was shown to be activated by the neurosteroid pregnenolone sulphate in pancreatic beta cell. The activation causes calcium influx and subsequent insulin release, therefore...

ion channel in hepatocytes and pancreatic islets causing calcium entry and subsequent insulin release.

Pituitary suppression

All corticosteroids have numerous and varied pharmacological actions. In humans, single dose or short term (several days) use is virtually without harmful effects. However prolonged therapeutic use of corticosteroids may result in suppression of the pituitary function. The daily threshold dose for this effect is approximately 0.5 mg for a 50 kg individual.

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