Basic Facts

Medical Studies on Pregnenolone – Basic Facts

Pregnenolon Grundlagen

Pregnenolone is considered to be the “grandmother” of all steroid hormones and its importance for human health has been acknowledged for decades. However, pregnenolone’s effectiveness is due not only to its metabolites but also to its role as an independent hormone; a role in which it fulfills important tasks – especially in the nervous system.

Rhythmic Release

Pregnenolone is produced in the brain, adrenal glands, liver and skin. Its production follows a daily rhythm, with peak values occurring around 8:00 in the morning and the lowest values present shortly before midnight. Like many other hormones, such as melatonin, pregnenolone levels decrease with age. For example, pregnenolone levels peak between the ages of 20 and 30 and decrease as we age. A 60- to 70-year-old, for example, only maintains 1/10 – 1/20 of the pregnenolone values obtained in younger years.

Complex Synthesis

The metabolism of pregnenolone follows a complex pathway. First, pregnenolone is formed from cholesterol in the mitochondria. Then it is further metabolized into progesterone, for example, and from here again into aldosterone or cortisol. Through another pathway, pregnenolone can become DHEA, where it can subsequently be metabolized into testosterone or estrogen. The conversion pathway pregnenolone takes is determined by the body and depends on various factors, such as isolated hormone deficiency, which causes pregnenolone to be converted in the body either to DHEA or to progesterone.

Interfering Factors in Pregnenolone Production

Age is not the only factor that can lead to a lack of pregnenolone. Chronic stress or illness can also create a deficit. Typical signs of low pregnenolone are fatigue, reduced performance, decreased memory and cognition, autoimmune concerns, or a dysfunctional immune system.

Medical Studies on Pregnenolone – Basic Facts

De novo neurosteroidogenesis in human microglia: involvement of the 18 kDa translocator protein

2021-03 Germelli L, Da Pozzo E, Giacomelli C, Tremolanti C, Marchetti L, Wetzel CH, Barresi E, Taliani S, Da Settimo F, Martini C, Costa B

Neuroactive steroids are potent modulators of microglial functions and are capable of counteracting their excessive reactivity. This action has mainly been ascribed to neuroactive steroids released from other sources, as microglia have been defined unable to produce neurosteroids de novo.

Site of action of brain neurosteroid pregnenolone sulfate at the N-Methyl-D-Aspartate Receptor

2020-07 Hrcka Krausova B, Kysilov B, Cerny J, Vyklicky V, Smejkalova T, Ladislav M, Balik A, Korinek M, Chodounska H, Kudova E, Vyklicky L

N-methyl-D-aspartate receptor (NMDAR) hypofunction has been implicated in several neurodevelopmental disorders. NMDAR function can be augmented by positive allosteric modulators, including endogenous compounds, such as cholesterol and neurosteroid pregnenolone sulfate (PES).

Steroids and TRP channels: a close relationship

2020-05 Méndez-Reséndiz KA, Enciso-Pablo Ó, González-Ramírez R, Juárez-Contreras R, Rosenbaum T, Morales-Lázaro SL

Transient receptor potential (TRP) channels are remarkable transmembrane protein complexes that are essential for the physiology of the tissues in which they are expressed. They function as non-selective cation channels allowing for the signal transduction of several chemical, physical and thermal stimuli and modifying cell function. These channels play pivotal roles in the nervous and reproductive systems, kidney, pancreas, lung, bone, intestine, among others.

Pregnenolone and pregnenolone-methyl-ether rescue neuronal defects caused by dysfunctional CLIP170 in a neuronal model of CDKL5 Deficiency Disorder

2020-03 Barbiero I, Peroni D, Siniscalchi P, Rusconi L, Tramarin M, De Rosa R, Motta P, Bianchi M, Kilstrup-Nielsen C

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are responsible for the onset of CDKL5 Deficiency Disorder (CDD), a neurological pathology characterised by severe infantile seizures, intellectual disability, impairment of gross motor skills, sleep and gastrointestinal disturbances. CDKL5 is a serine/threonine kinase the molecular network of which is not yet fully understood.

Effect of SULT2B1 genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by SULT2B1b allozymes

2019-10 Alherz FA, El Daibani AA, Abunnaja MS, Bairam AF, Rasool MI, Sakakibara Y, Suiko M, Kurogi K, Liu MC

Pregnenolone and dehydroepiandrosterone (DHEA) are hydroxysteroids that serve as biosynthetic precursors for steroid hormones in human body. SULT2B1b has been reported to be critically involved in the sulfation of pregnenolone and DHEA, particularly in the sex steroid-responsive tissues.

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