The biochemistry of steroids-what are steroids and what are they used to treat medically ?

From school children to medics nearly everyone has heard of a subgroup of hormones known as steroids. However if asked to define what a steroid is, few would get further than: something that has an effect on the body. So what exactly is a steroid? 

Chemically a steroid is any molecule that has a specific arrangement of cyclic carbons. Namely a steroid contains 3 cyclohexane structures and 1 cyclopentane. These are arranged in a specific order and if you wish to see this order simple google it. However when most of us talk about steroids what we really mean is steroid hormones, i.e. human hormones within the body that are steroids. Steroid hormones are subdivided into three types: Glucocorticoids, Mineralocorticoids, Androgens, Estrogens and Progestogens.

Generally our body synthesizes mineralocorticoids and glucocorticoids in the suprarenal (Adrenal) glands, which sit atop the kidney. Whilst Androgens, Estrogens and Progestogens are synthesized in the Gonads/Genitals. All five are synthesized from the sterol: Cholesterol. A Sterol is a steroid with a hydroxyl (-OH) functional group attached to the steroid structure. This gives the sterol a amphiphillic structure, i.e. it is both hydrophobic and hydrophillic, which is extremely important for cholesterols use in the cell membranes of cells.

So steroid hormones have a specific chemical structure and are synthesized from cholesterol. But what do thay actually do? Well the answer to this questions is predictably different for each steroid. However the subgroups of steroid hormones divide steroids into categories based on the repercussions they induce within the body. So:

Glucocorticoids – Glucocorticoids are a branch of steroids produced in the adrenal cortex and which bind to the Glucocorticoid receptors, which are present in nearly all vertebrate cells. Glucocorticoids have two major functions within the body; firstly as their name suggests they play a role in the regulation of glucose metabolism. Indeed Cortisol, which is the primary (main) glucocorticoid stimulates several processes, which serve to increase and maintain the glucose levels within the body. The first process by which it achieves this is gluconeogenesis, which occurs in the liver and generates glucose from non-carbohydrate molecules, such as glycerol, lactate and amino acids. The second main process is the inhibition of glucose uptake by muscle and adipose tissue (N.B. Adipose tissue = fat tissue) and thus the catabolism of fatty acids within muscle tissue instead of glucose.

Glucocorticoids also have anti-inflamatory properties and hence are used in medicine to treat allergies, asthma, autoimmune diseases and sepsis. A particularly potent anti-inflamatory is Prednisone, the active metabolite of which is prednisolone. Glucocorticoids achieve their antiinflamatory nature through two methods – firstly they up-regulate the expression and consequent production of anti-inflamatory proteins. This is achieved when the glucocorticoid binds to the glucocorticoid receptor and thus triggers the expression of antiinflamatory proteins in the nucleus a process known as transactivation  Secondly they down-regulate the expression of pro-inflamatory proteins, by preventing the translocation of transcription factors from the cytosol/cytoplasm to the nucleus, a process known as transregression.

Mineralocorticoids – Mineralocorticoids are the second division of steroid hormones generated within the adrenal cortex, leading to the mineralocorticoids and the glucocorticoids collectively being refered to as corticosteroids. However their functions are very different – Mineralocorticoids regulate water and salt content of the blood plasma. The primary mineralocorticoid is Aldosterone, which plays a key role in the Renin-Angiotensin-Aldosterone-System, which is a system that modulates the water content of the blood. I could write a whole article on the RAAS, but that is not the focus of this blog – so back to the specific role of Aldosterone. Aldosterone production is triggered through the RAAS and it results in the kidneys reabsorping more sodium ions within the distal convulated tubule of the nephrons. This reabsorption of sodium leads to water more water moving via osmosis back into the capillaries. Aldosterone also leads to a greater excretion of H+ cations (protons) and potassium ions out of the medulla of the kidneys and into the urea collecting ducts. In short mineralocorticoids control the amount of water and mineral retention in the kidneys and hence the water and mineral content of the blood.

Androgens – These are the Steroid hormones which promote the development and maintenance male characteristics in humans, this includes the development of the male sex organs and also the secondary sex characteristics. The primary androgen is testosterone and is produced in the testes. The production of testosterone as discussed in an earlier blog is mediated by LH from the Pituitary. The original main bulk of anabolic steroids were androgens and androgens are also important precursors to estrogens. 

Estrogens – Estrogens are the female sex steroid hormones. There are three types E1 – Estrone, which is present in post menopausal woman. E2 – Estradiol, present in unpregnant woman and produced by the developing follicles during the menstrual cycle. E3 – Estriol, present in pregnant woman. Estradiol is crucial for the building up of the endometrium, in preparation for embryo implantation.

Progestogens – Progestogens are a group of carbons with a 21-carbon skeleton, known as a pregnane skeleton. The two major Progestogens are Progesterone, which mains pregnancy and Pregnenolone, which acts as a precursor in the production of all other Steroid hormones.