Hormones are chemical messengers released into the blood, and how they travel depends mostly on one property: whether they mix with water. Some simply dissolve and drift along. Others hitch a ride on proteins that work like taxis. For the second group, most of the hormone in your blood at any moment is parked on its carrier and not doing anything, which is why some blood tests measure the small unbound share separately.
Water-Soluble Hormones Travel Freely
About 55% of blood is plasma, the watery liquid part, and plasma is 92% water.1Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones That suits hormones that dissolve in water. They can circulate unattached to anything, as so-called free hormones.2Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones This group includes protein-based hormones such as insulin and growth hormone, along with the adrenaline family of hormones.3Premier MCAT Prep. Transport & Amplification – MCAT Biology Like sugar stirred into tea, they simply spread through the liquid.
Because they dissolve freely, these hormones move around the body quickly.4Hormone Replacement Therapy. Water Soluble vs. Lipid Soluble Hormones The trade-off is that enzymes in the blood break them down rapidly, so most last only minutes.5Premier MCAT Prep. Transport & Amplification – MCAT Biology A short life suits a hormone like adrenaline, since a stress response needs to switch on fast and switch off soon after.
Cell membranes are fatty, like a thin film of oil, and water-soluble hormones can’t cross them. So they act by docking onto receptors on the cell’s surface.6N/A. Regulation of Hormone Action The hormone never enters; docking starts a chain of chemical signals inside the cell. One docking molecule can trigger many internal steps, so a tiny amount of hormone can produce a large response. Different cell types carry different receptors, which is why insulin changes muscle and fat cells but leaves many other cells largely unaffected.
Fat-Soluble Hormones Need a Carrier Protein
Hormones that dissolve in fat rather than water, such as the steroids cortisol, testosterone and estrogen, and thyroid hormone, must bind to carrier proteins in the blood.7Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones Binding to a protein effectively lets them mix with the watery plasma.8Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones About 90% of these hormones travel tightly bound to carriers.9Hormone Replacement Therapy. Water Soluble vs. Lipid Soluble Hormones So only about 0.1 to 10% of a fat-soluble hormone is unbound at any time.10Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones
These hormones are built mainly from fatty, oil-like chemistry, so in plain water they would clump together or stick to surfaces, much as oil beads up in water. The carrier acts as a water-friendly coat: its outside mixes with plasma while an inner pocket holds the hormone. Carrier proteins are mostly made by the liver, so liver health can influence how much carrier is available.
The carrier also protects the hormone. Kidneys filter blood by pushing small molecules out through tiny pores while keeping large proteins in. Steroid and thyroid hormones are small enough to pass those pores alone, but a hormone attached to a protein makes a package too big to get through. Carrier proteins stop these small hormones from being filtered out and lost in urine,11Integrated Human Anatomy and Physiology Part 2. Water-Soluble vs Lipid-Soluble Hormones which would otherwise happen to much of the hormone before it did any work.
Carriers also cushion the effect of sudden surges in hormone release,12Encyclopaedia Britannica. human endocrine system and they help spread a hormone evenly to all cells of large organs such as the liver.13Encyclopaedia Britannica. human endocrine system When free hormone is used up, more lets go of its carrier. Once free, a fat-soluble hormone can slip through cell membranes and act inside. Being shielded from breakdown and kidney loss also means steroids and thyroid hormone act over hours to days, not the minutes of freely travelling hormones.
The Main Carrier Proteins and What They Carry
- Sex hormone-binding globulin (SHBG): carries testosterone and estrogen, and your lab report may list it by that abbreviation.14PubMed. Potential functions of plasma steroid-binding proteins
- Corticosteroid-binding globulin: carries cortisol and is its main high-strength carrier.15PubMed. Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin
- Thyroid carriers: thyroid hormones T4 and T3 travel mainly on thyroxine-binding globulin (TBG), transthyretin and albumin.16Encyclopedia of Life Sciences. Genetics of Thyroid Hormone‐Binding Proteins
- Albumin: the most plentiful protein in plasma, it carries many hormones loosely.17PubMed. Directional thyroid hormone distribution via the blood stream to target sites
- Vitamin D-binding protein: vitamin D, which acts like a hormone, has its own carrier.18PubMed Central. Vitamin D Binding Protein: A Historic Overview
A lab may list a carrier alongside a hormone because the carrier level helps interpret the hormone’s total result. Albumin rarely gets its own hormone test, but it influences how much hormone sits loosely bound.
Carriers differ in how tightly they grip. TBG holds thyroid hormone most tightly of the three thyroid carriers, and the others can’t make up for a shortage of TBG, which shows it does most of the work.19PubMed. Directional thyroid hormone distribution via the blood stream to target sites Some carriers may also help steer hormones to particular tissues, such as sites of inflammation, rather than just ferrying them.20PubMed. Potential functions of plasma steroid-binding proteins Specific carriers grip tightly but there is little of each; albumin grips loosely but there is a lot of it, so hormone on albumin lets go more easily.
Growth hormone is an exception to the water-and-fat pattern. It dissolves in water yet still has a binding protein, which keeps it in the bloodstream and slows its breakdown. The water/fat rule is a strong tendency, not an absolute.
Free Versus Total Hormone on a Blood Test
The working idea in medicine is that a hormone’s effect depends on its free hormone level, the unbound share, rather than the total.21PubMed. The free hormone hypothesis: a physiologically based mathematical model For testosterone, the balance between free and total is set by SHBG and albumin.22PubMed Central. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology
On a report, total is all the hormone, bound plus unbound. Free is the small unbound share that tissues can use. A high carrier level can raise total while free stays normal, so doctors look at both when results don’t fit symptoms.
Anything that raises SHBG or TBG pulls more hormone into the bound pool. The body may then release more to keep free levels steady, so a total level alone can look abnormal while you feel fine. A high total alone does not mean excess hormone effect. Carrier levels can rise or fall with conditions or treatments, including liver disease, pregnancy and some medicines such as estrogen-containing pills.
For testing, total testosterone is best measured in the morning while fasting, using a reliable lab method.23PubMed. Accurate measurement of total and free testosterone levels for the diagnosis of androgen disorders Free testosterone is worth checking when carrier levels may be off or total testosterone is borderline.24PubMed. Accurate measurement of total and free testosterone levels for the diagnosis of androgen disorders
Thyroid testing has its own wrinkle: common thyroid hormone tests can read T3 as normal when a more accurate method shows it low.25PubMed Central. How reliable are free thyroid and total T3 hormone assays? In one group of hospital patients on several medicines, 48% had low T3 by the accurate method versus 11% by the standard test.26PubMed Central. How reliable are free thyroid and total T3 hormone assays? If you still feel hypothyroid symptoms with normal results, it’s reasonable to ask your doctor about the testing method.
How Hormones Leave the Blood and Reach Cells
The journey starts when a gland releases hormone into nearby capillaries. It travels free or bound through the circulation, exits through gaps or by vesicle transport in the vessel wall, and finally binds a receptor on or inside the target cell.
The vessel wall is the barrier in the middle. In some tissues hormones pass through large pores in the wall, while elsewhere only small molecules leak between cells.27PubMed Central. The Barrier Within: Endothelial Transport of Hormones Capillaries in organs such as endocrine glands and kidneys have pores that let molecules through easily, which suits organs that exchange a lot with blood. Capillaries in the brain form a much tighter seal and let through far less, so the same hormone may reach some tissues readily and others slowly. Inflammation opens the gaps between vessel-wall cells, letting more through.28PubMed Central. The Barrier Within: Endothelial Transport of Hormones
Larger protein hormones are carried through the wall cells inside small bubbles called vesicles.29PubMed Central. The Barrier Within: Endothelial Transport of Hormones A vessel-wall cell wraps a pocket of its outer membrane around the hormone and pulls it inward. The bubble crosses the cell and opens on the far side, releasing the hormone into the tissue fluid. That is slower than leaking between cells, but it lets through large molecules that could not squeeze past the gaps. A pregnancy-type hormone, hCG, crossed vessel cells this way within about 20 minutes in animal tissue.30PubMed Central. How protein hormones reach their target cells. Receptor-mediated transcytosis of hCG through endothelial cells Leptin, the appetite hormone, also crosses vessel walls through the cells rather than between them.31PubMed Central. The Barrier Within: Endothelial Transport of Hormones
Some bound hormones may be taken up along with their carrier. Animals lacking a particular cell-surface protein become insensitive to sex hormones,32PubMed. “Bound” to work: the free hormone hypothesis revisited which suggests some cells swallow hormone still attached to its carrier, not only free hormone.
What Can Change Hormone Transport
Hormones like cortisol and thyroid hormone can be pushed off their carriers by drugs.33PubMed Central. Displacement of One Drug by Another from Carrier or Receptor Sites At usual doses, danazol could displace about 83% of carrier-bound testosterone and methyltestosterone about 48%.34PubMed. Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma The steroid prednisolone could lower carrier-bound cortisol by about 32%.35PubMed. Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma
A carrier has a limited number of binding sites, so a drug that fits the same site can crowd a hormone off it. How much a drug displaces depends on the drug, the dose and how tightly it grips compared with the hormone. A drug’s effect on one carrier doesn’t imply the same on another.
Displaced hormone is cleared faster, so the total can read lower even though the gland is working normally and free hormone stays near normal. Steroid and hormone medicines are the most likely culprits, which is why it helps to tell your doctor about all your medicines, including supplements, before hormone blood tests.
Pregnancy and exercise matter too. Pregnancy hormones change the levels of several transport proteins in liver cells grown in the lab.36PubMed Central. Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes Moderate long endurance exercise raises free testosterone, but not by loosening SHBG’s grip.37PubMed. Effects of endurance exercise on free testosterone concentration and the binding affinity of sex hormone binding globulin (SHBG)
Newer Discoveries in Hormone Signalling
Cells also release tiny fat-wrapped bubbles called extracellular vesicles, which carry proteins, fats and genetic material through body fluids.38PubMed Central. A Novel “Endocrine Hormone”: The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance Unlike a single-molecule hormone, one vesicle can deliver a mixed set of instructions.39PubMed Central. A Novel “Endocrine Hormone”: The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance Its fatty skin protects the contents from enzymes in the blood, and a receiving cell may use what’s inside to change its own activity. Most cell types release them, so they circulate in large numbers.
The placenta sends vesicles carrying instructions for a stress hormone into the mother’s blood late in pregnancy.40PubMed. Human placenta releases extracellular vesicles carrying corticotrophin releasing hormone mRNA into the maternal blood These vesicles are also being studied for a role in insulin resistance across organs.41PubMed Central. A Novel “Endocrine Hormone”: The Diverse Role of Extracellular Vesicles in Multiorgan Insulin Resistance Researchers are asking whether they help organs such as fat, liver and muscle coordinate with each other. The work is early and doesn’t change routine blood tests yet.