biology

Neurosteroid

Neurosteroid is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Neurosteroid rather than just read about it. In short: Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain.

Key takeaways

Neurosteroid belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Neurosteroid to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Neurosteroid from memory before moving on to harder problems.

Reference excerpt

Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy.

Classification

Based on differences in activity and structure, neurosteroids can be broadly categorized into several different major groupings.

Inhibitory neurosteroids These neurosteroids exert inhibitory actions on neurotransmission. They act as positive allosteric modulators of the GABAA receptor (especially δ subunit-containing isoforms), and possess, in no particular order, antidepressant, anxiolytic, stress-reducing, rewarding, prosocial, antiaggressive, prosexual, sedative, pro-sleep, cognitive and memory-impairing, analgesic, anesthetic, anticonvulsant, neuroprotective, and neurogenic effects. Major examples include tetrahydrodeoxycorticosterone (THDOC), the androstane 3α-androstanediol, the cholestane cholesterol and the pregnanes pregnanolone (eltanolone), allopregnanolone (3α,5α-THP).

Excitatory neurosteroids These neurosteroids have excitatory effects on neurotransmission. They act as potent negative allosteric modulators of the GABAA receptor, weak positive allosteric modulators of the NMDA receptor, and/or agonists of the σ1 receptor, and mostly have antidepressant, anxiogenic, cognitive and memory-enhancing, convulsant, neuroprotective, and neurogenic effects. Major examples include the pregnanes pregnenolone sulfate (PS), epipregnanolone, and isopregnanolone (sepranolone), the androstanes dehydroepiandrosterone (DHEA; prasterone), and dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate), and the cholestane 24(S)-hydroxycholesterol (NMDA receptor-selective; very potent).

Pheromones

Pheromones are neurosteroids that influence brain activity, notably hypothalamic function, via activation of vomeronasal receptor cells. Possible human pheromones include the androstanes androstadienol, androstadienone, androstenol, and androstenone and the estrane estratetraenol.

Other neurosteroids Certain other endogenous steroids, such as pregnenolone, progesterone, estradiol, and corticosterone are also neurosteroids. However, unlike those listed above, these neurosteroids do not modulate the GABAA or NMDA receptors, and instead affect various other cell surface receptors and non-genomic targets. Also, many endogenous steroids, including pregnenolone, progesterone, corticosterone, deoxycorticosterone, DHEA, and testosterone, are metabolized into (other) neurosteroids, effectively functioning as so-called proneurosteroids.

Biosynthesis Neurosteroids are synthesized from cholesterol, which is converted into pregnenolone and then into all other endogenous steroids. Neurosteroids are produced in the brain after local synthesis or by conversion of peripherally-derived adrenal steroids or gonadal steroids. They accumulate especially in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. 5α-reductase type I and 3α-hydroxysteroid dehydrogenase are involved in the biosynthesis of inhibitory neurosteroids, while 3β-hydroxysteroid dehydrogenase and hydroxysteroid sulfotransferases are involved in excitatory neurosteroid production.

Function Some major known biological functions of neurosteroids include modulation of neural plasticity, learning and memory processes, behavior, and seizure susceptibility, as well as responses to stress, anxiety, and depression. Neurosteroids also appear to play an important role in various sexually-dimorphic behaviors and emotional responses. Acute stress elevates the levels of inhibitory neurosteroids like allopregnanolone, and these neurosteroids are known to counteract many of the effects of stress. This is similar to the case of endorphins, which are released in response to stress and physical pain and counteract the negative subjective effects of such states. As such, it has been suggested that one of the biological functions of these neuromodulators may be to help maintain emotional homeostasis. Chronic stress has been associated with diminished levels of allopregnanolone and altered allopregnanolone stress responsivity, psychiatric disorders, and hypothalamic-pituitary-adrenal axis dysregulation. It is thought that fluctuations in the levels of inhibitory neurosteroids during the menstrual cycle and pregnancy play an important role in a variety of women's conditions, including premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), postpartum depression (PPD), postpartum psychosis, and catamenial epilepsy. In addition, it is thought that changes in neurosteroid levels may be involved in the changes in mood, anxiety, and sexual desire that occur during puberty in both sexes and during menopause in women. Elevated levels of inhibitory neurosteroids, namely allopregnanolone, can produce paradoxical effects, such as negative mood, anxiety, irritability, and aggression. This appears to be because these neurosteroids, like other positive allosteric modulators of the GABAA receptor such as the benzodiazepines, barbiturates, and ethanol, possess biphasic, U-shaped actions – moderate levels (in the range of 1.5–2 nM/L total alloprogesterone, which are approximately equivalent to luteal phase levels) inhibit the activity of the GABAA receptor, while lower and higher concentrations facilitate the activity of the receptor.

Biological activity

Sigma-1 receptor

Therapeutic applications

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Neurosteroid

Start with the simplest possible case. Write down what Neurosteroid claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Neurosteroid before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Neurosteroid ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Neurosteroid

In research: Neurosteroid appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Neurosteroid in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Neurosteroid is common in secondary-school and first-year university syllabi. It links to neighbouring topics Neurophysiology, Neurosteroids, so understanding it makes those chapters shorter.
In everyday life: Look for Neurosteroid outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Neurosteroid in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Neurosteroid means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Neurosteroid out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Neurosteroid in simple terms?

Why does Neurosteroid matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Neurosteroid?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Neurosteroid.