Adrenal Hormone Synthesis
by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. L2 Strength & Conditioning Coach.
There are a number of steps that go into adrenal hormone synthesis. Here's a look at the genes involved. This article discusses the different steps in adrenal steroid hormone synthesis, including cholesterol transport and regulation. You can also learn about the different enzymes involved and the ways that these hormones can be altered.
What Are Adrenal Hormones?
The body's natural response to stress is to produce adrenal hormones, and they help the body deal with stressful events. When people get a severe illness, for example, their adrenal glands will automatically produce about 10 times more cortisol than usual. But sometimes the body does not make enough of these hormones, so replacement medications must be used.
The adrenal gland produces a number of steroid hormones, including adrenaline and noradrenaline, which regulate blood pressure, heart rate, and other bodily functions. These glands sit on top of each kidney, and they contain the spinal cord, brain, and nerves. The adrenal glands are shaped like a triangular triangle.
Patients with adrenal gland problems often display a wide range of symptoms. The severity of these symptoms depends on which hormones are affected. Many symptoms are similar to those of other illnesses, including unexplained weight gain, frequent high or low blood sugar, fatigue, and immune system dysfunction. Males may also experience problems with their sexual characteristics, and prepubescent males may develop facial hair.
There are many diseases and disorders of the adrenal glands. Some cause chronic damage, while others are temporary and reversible. The damage can be caused by a tumor or by an infection. Moreover, certain medications can damage the adrenal glands, causing imbalances in production of hormones.
How to Determine Adrenal Hormones
The adrenal glands are located above the kidneys and secrete several hormones that are needed to maintain a healthy body. If these glands are not functioning properly, this can cause many problems. The most important hormone is cortisol, which helps the body respond to stressful situations and recover from infections. It also helps maintain normal blood pressure and regulates the metabolism of carbohydrates, proteins, and salt. The other hormone is aldosterone, which helps maintain water and potassium balance in the body.
Adrenal hormones are a class of hormones that regulate body functions. They can also cause diseases. There are various methods for the determination of adrenal hormones. One of these methods is the chromaffin cell culture technique, which allows the isolation of the adrenals from the body. This method also allows simultaneous analysis of the hormones, enzyme activities, and proteins.
Another way to identify adrenal insufficiency is to perform ultrasound, CT scan, or MRI. The results of these tests will help determine whether the patient has a mass in the adrenal gland. In some cases, the mass may be causing excessive levels of the hormone, and it should be treated accordingly.
Genes involved in adrenal steroid hormone synthesis
Steroid hormone synthesis takes place in the adrenal cortex. Several genes are involved in the process. These include CYP11A1, which converts cholesterol to the steroid hormone pregnenolone. Another important gene is HSD3B2, which is involved in the synthesis of all steroid hormones. STAR is also involved in the process, and is expressed at higher levels in the adrenal cortex.
The Fabp6 gene was also identified as being significantly upregulated during the regeneration of the adrenals. Interestingly, Fabp6 was also detected in the steroid-producing cells. This gene may have a role in transporting and metabolizing fatty acids necessary for steroid hormone synthesis.
Besides corticosteroids, the adrenal gland also produces other hormones. The outermost cortex produces noradrenalin and adrenalin, while the middle and inner adrenal cortex produce glucocorticoids and sex hormones. The mRNA levels of the genes in these tissues are elevated four-fold in the adrenal gland compared to the genes in other tissues.
Two distinct types of rats are used to study adrenal steroid hormone synthesis. These include the Milan hypertensive rat and the Dahl salt-sensitive rat. Both models have distinct genetic loci that contribute to the development of hypertension. The development of both types of hypertension is exacerbated by sodium loading, making it possible to study the pathogenesis of these disorders.
In addition to the adrenal gland, these genes have been identified in other tissues, including thyroid, ovarian, and skeletal muscle. The gene expression levels were determined by a hierarchical clustering algorithm. A network plot was constructed using this method. The enriched genes are highlighted on a heat map. The nodes represent the genes that are expressed in the different tissues, with green being the most expressed and red being the least expressed.
Steps in steroid hormone synthesis
The biosynthesis of adrenal hormones involves three steps. First, a hormone called progesterone is converted to 17-hydroxyprogesterone. Afterward, a second hormone called cortisol is synthesized. This hormone acts on the receptors on melanocortin 2 cells to activate these cells.
This process is called metabolic activation. It is an essential step because it involves converting steroids to their active forms before they can interact with receptors. The rate at which these steroids are converted to their active forms determines the effects that they have on the cells. The rate at which a steroid acts on its receptors is also affected by the environment.
Steroid hormones are lipophilic, low-molecular-weight organic compounds. They are synthesized in endocrine glands and are released into the bloodstream. They regulate nearly every metabolic process in the body. In addition, their function is tissue-specific.
Steroid hormones are transported throughout the blood by carrier proteins. These proteins increase the solubility of the hormones in the blood. Examples of carrier proteins include albumin, sex hormone-binding globulin, and corticosteroid-binding globulin. Steroid hormones then must free themselves from these carrier proteins and then passively cross the cell membrane to reach their nuclear receptors. This is known as the free hormone hypothesis.
Interestingly, there is a correlation between aging and a decline in steroid hormone production. This has been observed in laboratory animals. This is the result of inadequate cholesterol availability during the first step of steroid hormone biosynthesis. This first step involves the conversion of cholesterol into pregnenolone by the P450scc enzyme system, or CYP11A1.
Regulation of steroid hormone synthesis by cholesterol transport
Cholesterol is a versatile lipid, an integral component of all subcellular membranes, and a precursor substrate for the synthesis of all steroid hormones. It accounts for about 30% of the total cellular lipid content and about 60 to 80% of the total cholesterol in plasma membranes. Its concentration varies widely among different membrane types, ranging from 0.5 to 1% in the Golgi apparatus to as high as 60% in the plasma membrane.
Cholesterol transport plays a critical role in the regulation of steroid hormone synthesis. Cholesterol is synthesized from acetyl coenzyme A and is the preferred source of cholesterol for steroid-producing cells. It is found in both low-density lipoprotein (LDL) and high-density lipoproteins (HDL). LDL particles containing cholesterol bind to the LDL receptors on the plasma membranes of steroid-producing cells, such as ovarian and adrenocortical cells. During steroidogenesis, luteinizing hormone and adrenocortical hormone increase the uptake of LDL in these cells.
During hormone stimulation, cholesterol synthesis is tightly regulated within the ER. Cholesterol transport out of the ER involves multiple pathways, including passive diffusion and intracellular compartments. Contact sites between the ER and other intracellular organelles include stacks of mitochondria, which cluster with ER and other intracellular organelles. Cholesterol produced in the ER might use these contact sites to enter the mitochondria.
In addition to binding to the ER, TSPO also regulates cholesterol transport through the ER. Although this pathway does increase cholesterol levels, it has not been proven to be the primary pathway for steroid hormone synthesis. This pathway may play a role in steroid hormone production, but further studies are needed to clarify this relationship.
Adrenal Hormone Synthesis Conclusion
Adrenal hormone synthesis is regulated by a number of enzymes in the adrenal cortex. The adrenal cortex has three main tissue zones, the zona glomerulosa, zona fasciculata, and zona reticularis. These zones are histologically and enzymatically distinct, and the products of steroid hormone synthesis depend on the enzymes present in each zone.
The HSD3B2 gene encodes a bi-functional enzyme that functions as a 3b-hydroxysteroid dehydrogenase and a D4,5-isomerase. It is also a 21-hydroxylase, which has two substrate binding sites. It is responsible for converting 17a-hydroxyprogesterone to 11-deoxycortisol. Mutations in the CYP21A2 gene cause congenital adrenal hyperplasia.
The main glucocorticoid hormone produced by the adrenal cortex is aldosterone. It is synthesized from pregnenolone by the zona reticularis cells. This hormone is produced from the enzyme P450ssc (CYP11A1) in the mitochondria. The enzyme is also responsible for converting pregnenolone to progesterone.
To synthesize steroid hormones, cholesterol has to be transported from the outer mitochondrial membrane to the inner mitochondrial membrane. This process is mediated by a steroidogenic acute regulatory protein, or STAR. This gene is exclusively expressed in adult adrenal cortical cells.