Steroids are biologically active compounds composed of four fused rings. Although the word “steroid” is commonly associated with anabolic steroids and muscle growth, steroids are in fact a diverse group of compounds with varying effects on the human body.
The steroid cholesterol can be either synthesized via the mevalonate pathway or are obtained from the diet. The mevalonate pathway starts with acetyl-CoA, which is converted in a series of steps to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are the building blocks of isoprenoids, a diverse group of compounds that include steroids. The enzyme HMG-CoA reductase, which catalyzes the step converting HMG-CoA to mevalonate, is blocked by statins which are used for the treatment of high cholesterol levels. The IPP units are combined to form farnesyl pyrophosphate, which are then used to form squalene. From there, the squalene is cyclized to form lanosterol, which is then converted to cholesterol. Cholesterol is important for moderating cell membrane fluidity, and also participates in the formation of lipid rafts which are theorized to be involved in cell signalling. [1]
Cholesterol can then be converted into a variety of signalling molecules such as neurosteroids, vitamin D, glucocorticoids, mineralocorticoids, and sex steroids. Neurosteroids modulate complex activities in the brain, such as neural plasticity. They can act in an excitatory manner (such as dehydroepiandrosterone (DHEA), which modulates NMDA receptor activity) or inhibitory manner (such as pregnanolone, which modulates GABA A receptor activity). [2]
Vitamin D is involved in calcium homeostasis, increasing calcium absorption in the intestines and modulating bone remodulating. It is synthesized from cholesterol, including a step that involves UV radiation. It is then hydroxylated twice in order to be in the active form, 1,25-dihydroxycholecalciferol, also known as calcitriol, which binds to the vitamin D receptor to produce its effects. [3]
Glucocorticoids such as cortisol modulate metabolism and immune function. Cortisol promotes gluconeogenesis, which produces glucose, as well as promoting the breakdown of lipids and proteins. It also diminishes immune function by inhibiting the effects of various cytokines that promote inflammation and immune responses. [4]
Mineralocorticoids such as aldosterone helps to maintain blood pressure and electrolyte balance. Aldosterone acts in the kidneys to increase sodium reabsorption and potassium excretion, thus increasing sodium levels and decreasing potassium levels in the blood. Because of the sodium reabsorption, water is then retained, increasing blood volume and thus increasing blood pressure. Glucocorticoids and mineralocorticoids are both synthesized from cholesterol via progestogens in the adrenal cortex by 21-hydroxylase and 11β-hydroxylase. [5]
Sex steroids are classified as progestogens (such as progesterone), androgens (such as testosterone), or estrogens (such as estradiol). Estrogens are synthesized from androgens by the enzyme aromatase, while androgens are synthesized from progestogens by 17α-hydroxylase. Progestogens are synthesized by the conversion of cholesterol by cholesterol side-chain cleavage enzyme. Sex steroids regulate a variety of activities. Progesterone is important in the secretory phase of the uterus during the menstrual cycle, where it is produced by the corpus luteum to maintain the endometrial lining for implantation. Testosterone is important for sperm development, as well as increasing muscle growth and contributing to male secondary sex characteristics. Estradiol is responsible for inducing ovulation, bone maintenance, and female secondary sex characteristics. However, all sex steroids have diverse roles in people of all genders that are not described here. [6][7][8]
Steroids are a diverse group of compounds, and this is only the beginning. You can read about more steroids here!
Sources:
[1] Russell, D. W. (1992). Cholesterol biosynthesis and metabolism. Cardiovascular Drugs and Therapy, 6(2), 103–110. https://doi.org/10.1007/BF00054556
[2] Robel, P., & Baulieu, E. E. (1995). Neurosteroids: Biosynthesis and function. Critical Reviews in Neurobiology, 9(4), 383–394.
[3] Bikle, D. (2000). Vitamin D: Production, Metabolism, and Mechanisms of Action. In K. R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, W. W. de Herder, K. Dhatariya, K. Dungan, A. Grossman, J. M. Hershman, J. Hofland, S. Kalra, G. Kaltsas, C. Koch, P. Kopp, M. Korbonits, C. S. Kovacs, W. Kuohung, B. Laferrère, E. A. McGee, … D. P. Wilson (Eds.), Endotext. MDText.com, Inc. http://www.ncbi.nlm.nih.gov/books/NBK278935/
[3] Arlt, W., & Stewart, P. M. (2005). Adrenal corticosteroid biosynthesis, metabolism, and action. Endocrinology and Metabolism Clinics of North America, 34(2), 293–313, viii. https://doi.org/10.1016/j.ecl.2005.01.002
[5] Connell, J. M., Fraser, R., & Davies, E. (2001). Disorders of mineralocorticoid synthesis. Best Practice & Research. Clinical Endocrinology & Metabolism, 15(1), 43–60. https://doi.org/10.1053/beem.2000.0118
[6] Aizawa, K., Iemitsu, M., Maeda, S., Jesmin, S., Otsuki, T., Mowa, C. N., Miyauchi, T., & Mesaki, N. (2007). Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats. American Journal of Physiology. Endocrinology and Metabolism, 292(2), E577-584. https://doi.org/10.1152/ajpendo.00367.2006
[7] Penning, T. M. (2010). New Frontiers in Androgen Biosynthesis and Metabolism. Current Opinion in Endocrinology, Diabetes, and Obesity, 17(3), 233–239. https://doi.org/10.1097/MED.0b013e3283381a31
[8] Cui, J., Shen, Y., & Li, R. (2013). Estrogen synthesis and signaling pathways during ageing: From periphery to brain. Trends in Molecular Medicine, 19(3), 197–209. https://doi.org/10.1016/j.molmed.2012.12.007
