Steroid hormone
Steroid hormone | ||
---|---|---|
Chemical class Steroidal; Nonsteroidal | | |
Legal status | ||
In Wikidata |
A steroid hormone is a
Steroid hormones help control
Synthesis
The natural steroid hormones are generally synthesized from
Sex | Sex hormone | Reproductive phase |
Blood production rate |
Gonadal secretion rate |
Metabolic clearance rate |
Reference range (serum levels) | |
---|---|---|---|---|---|---|---|
SI units | Non-SI units | ||||||
Men | Androstenedione | –
|
2.8 mg/day | 1.6 mg/day | 2200 L/day | 2.8–7.3 nmol/L | 80–210 ng/dL |
Testosterone | –
|
6.5 mg/day | 6.2 mg/day | 950 L/day | 6.9–34.7 nmol/L | 200–1000 ng/dL | |
Estrone | –
|
150 μg/day | 110 μg/day | 2050 L/day | 37–250 pmol/L | 10–70 pg/mL | |
Estradiol | –
|
60 μg/day | 50 μg/day | 1600 L/day | <37–210 pmol/L | 10–57 pg/mL | |
Estrone sulfate | –
|
80 μg/day | Insignificant | 167 L/day | 600–2500 pmol/L | 200–900 pg/mL | |
Women | Androstenedione | –
|
3.2 mg/day | 2.8 mg/day | 2000 L/day | 3.1–12.2 nmol/L | 89–350 ng/dL |
Testosterone | –
|
190 μg/day | 60 μg/day | 500 L/day | 0.7–2.8 nmol/L | 20–81 ng/dL | |
Estrone | Follicular phase | 110 μg/day | 80 μg/day | 2200 L/day | 110–400 pmol/L | 30–110 pg/mL | |
Luteal phase | 260 μg/day | 150 μg/day | 2200 L/day | 310–660 pmol/L | 80–180 pg/mL | ||
Postmenopause | 40 μg/day | Insignificant | 1610 L/day | 22–230 pmol/L | 6–60 pg/mL | ||
Estradiol | Follicular phase | 90 μg/day | 80 μg/day | 1200 L/day | <37–360 pmol/L | 10–98 pg/mL | |
Luteal phase | 250 μg/day | 240 μg/day | 1200 L/day | 699–1250 pmol/L | 190–341 pg/mL | ||
Postmenopause | 6 μg/day | Insignificant | 910 L/day | <37–140 pmol/L | 10–38 pg/mL | ||
Estrone sulfate | Follicular phase | 100 μg/day | Insignificant | 146 L/day | 700–3600 pmol/L | 250–1300 pg/mL | |
Luteal phase | 180 μg/day | Insignificant | 146 L/day | 1100–7300 pmol/L | 400–2600 pg/mL | ||
Progesterone | Follicular phase | 2 mg/day | 1.7 mg/day | 2100 L/day | 0.3–3 nmol/L | 0.1–0.9 ng/mL | |
Luteal phase | 25 mg/day | 24 mg/day | 2100 L/day | 19–45 nmol/L | 6–14 ng/mL | ||
Notes and sources
Notes: "The concentration of a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. The secretion rate of a steroid refers to the total secretion of the compound from a gland per unit time. Secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. The metabolic clearance rate of a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. The production rate of a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. At steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). If there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate." Sources: See template. |
Synthetic steroids and sterols
A variety of synthetic steroids and sterols have also been contrived. Most are steroids, but some nonsteroidal molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker or stronger than the natural steroids whose receptors they activate.[8]
Some examples of synthetic steroid hormones:
- Glucocorticoids: alclometasone, prednisone, dexamethasone, triamcinolone, cortisone
- Mineralocorticoid: fludrocortisone
- Vitamin D: dihydrotachysterol
- Androgens: oxandrolone, oxabolone, nandrolone (also known as anabolic-androgenic steroids or simply anabolic steroids)
- Oestrogens: diethylstilbestrol (DES) and ethinyl estradiol (EE)
- Progestins: norethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate.
Some steroid antagonists:
- Androgen: cyproterone acetate
- Progestins: mifepristone, gestrinone
Transport
Steroid hormones are transported through the blood by being bound to carrier proteins—serum proteins that bind them and increase the hormones' solubility in water. Some examples are
One study has found that these steroid-carrier complexes are bound by megalin, a membrane receptor, and are then taken into cells via endocytosis. One possible pathway is that once inside the cell these complexes are taken to the lysosome, where the carrier protein is degraded and the steroid hormone is released into the cytoplasm of the target cell. The hormone then follows a genomic pathway of action. This process is shown in Figure 2 to the right.[10] The role of endocytosis in steroid hormone transport is not well understood and is under further investigation.
In order for steroid hormones to cross the lipid bilayer of cells, they must overcome energetic barriers that would prevent their entering or exiting the membrane. Gibbs free energy is an important concept here. These hormones, which are all derived from cholesterol, have hydrophilic functional groups at either end and hydrophobic carbon backbones. When steroid hormones are entering membranes free energy barriers exist when the functional groups are entering the hydrophobic interior of membrane, but it is energetically favorable for the hydrophobic core of these hormones to enter lipid bilayers. These energy barriers and wells are reversed for hormones exiting membranes. Steroid hormones easily enter and exit the membrane at physiologic conditions. They have been shown experimentally to cross membranes near a rate of 20 μm/s, depending on the hormone.[11]
Though it is energetically more favorable for hormones to be in the membrane than in the ECF or ICF, they do in fact leave the membrane once they have entered it. This is an important consideration because cholesterol—the precursor to all steroid hormones—does not leave the membrane once it has embedded itself inside. The difference between cholesterol and these hormones is that cholesterol is in a much larger negative Gibb's free energy well once inside the membrane, as compared to these hormones. This is because the aliphatic tail on cholesterol has a very favorable interaction with the interior of lipid bilayers.[11]
Mechanisms of action and effects
There are many different mechanisms through which steroid hormones affect their target cells. All of these different pathways can be classified as having either a genomic effect or a non-genomic effect. Genomic pathways are slow and result in altering transcription levels of certain proteins in the cell; non-genomic pathways are much faster.
Genomic pathways
The first identified mechanisms of steroid hormone action were the genomic effects.[12] In this pathway, the free hormones first pass through the cell membrane because they are fat soluble.[7] In the cytoplasm, the steroid may or may not undergo an enzyme-mediated alteration such as reduction, hydroxylation, or aromatization. Then the steroid binds to a specific steroid hormone receptor, also known as a nuclear receptor, which is a large metalloprotein. Upon steroid binding, many kinds of steroid receptors dimerize: two receptor subunits join together to form one functional DNA-binding unit that can enter the cell nucleus. Once in the nucleus, the steroid-receptor ligand complex binds to specific DNA sequences and induces transcription of its target genes.[4][13][14][12]
Non-genomic pathways
Because non-genomic pathways include any mechanism that is not a genomic effect, there are various non-genomic pathways. However, all of these pathways are mediated by some type of
See also
References
- ^ "Steroid hormones - Latest research and news | Nature". www.nature.com. Retrieved 2021-12-06.
- ^ "steroid hormone | Definition, Classification, & Function | Britannica". www.britannica.com. Retrieved 2021-12-06.
- PMID 9238855.
- ^ a b Gupta BBP, Lalchhandama K (2002). "Molecular mechanisms of glucocorticoid action" (PDF). Current Science. 83 (9): 1103–1111.
- PMID 19942840.
- ISSN 2002-4436.
- ^ ISBN 978-1-4051-9452-5. Retrieved 28 November 2010.
- PMID 17504217.
- PMID 16143095.
- PMID 16143106.
- ^ PMID 15298886.
- ^ S2CID 24346074.
- S2CID 1998076.
- PMID 12422243.
- PMID 25257522.
Further reading
- Brook CG (1999). "Mechanism of puberty". Horm. Res. 51 Suppl 3 (3): 52–4. S2CID 33671883.
- Holmes SJ, Shalet SM (1996). "Role of growth hormone and sex steroids in achieving and maintaining normal bone mass". Horm. Res. 45 (1–2): 86–93. PMID 8742125.
- Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, Forabosco A, Schlessinger D (Jan 2007). "Determination and stability of sex". BioEssays. 29 (1): 15–25. S2CID 23824870.
- Couse JF, Korach KS (June 1998). "Exploring the role of sex steroids through studies of receptor deficient mice". J. Mol. Med. 76 (7): 497–511. S2CID 6470903.
- McEwen BS (1992). "Steroid hormones: effect on brain development and function". Horm. Res. 37 Suppl 3 (3): 1–10. PMID 1330863.
- Simons (Aug 2008). "physiological versus pharmacological steroid hormone actions". BioEssays. 30 (8): 744–56. PMID 18623071.
- Han, Thang S.; Walker, Brian R.; Arlt, Wiebke; Ross, Richard J. (17 December 2013). "Treatment and health outcomes in adults with congenital adrenal hyperplasia". Nature Reviews Endocrinology. 10 (2): 115–124. S2CID 6090764Figure 2: The adrenal steroidogenesis pathway.)
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