Intracrine refers to a hormone that acts inside a cell, regulating intracellular events. In simple terms it means that the cell stimulates itself by cellular production of a factor that acts within the cell. Steroid hormones act through intracellular (mostly nuclear) receptors and, thus, may be considered to be intracrines. In contrast, peptide or protein hormones, in general, act as endocrines, autocrines, or paracrines by binding to their receptors present on the cell surface. Several peptide/protein hormones or their isoforms also act inside the cell through different mechanisms. These peptide/protein hormones, which have intracellular functions, are also called intracrines. The term 'intracrine' is thought to have been coined to represent peptide/protein hormones that also have intracellular actions. To better understand intracrine, we can compare it to paracrine, autocrine and endocrine. The autocrine system deals with the autocrine receptors of a cell allowing for the hormones to bind, which have been secreted from that same cell. The paracrine system is one where nearby cells get hormones from a cell, and change the functioning of those nearby cells. The endocrine system refers to when the hormones from a cell affect another cell that is very distant from the one that released the hormone.
Paracrine physiology has been understood for decades now and the effects of paracrine hormones have been observed when for example, an obesity associate tumor will face the effects of local adipocytes, even if it is not in direct contact with the fat pads in concern. [1] Endocrine physiology on the other hand is a growing field and has had a new area explored, called intracrinology. In intracrinology, the sex steroids produced locally, exert their action in the same cell where they are produced. [2]
The biological effects produced by intracellular actions are referred as intracrine effects, whereas those produced by binding to cell surface receptors are called endocrine, autocrine, or paracrine effects, depending on the origin of the hormone. The intracrine effect of some of the peptide/protein hormones are similar to their endocrine, autocrine, or paracrine effects; however, these effects are different for some other hormones.
Intracrine can also refer to a hormone acting within the cell that synthesizes it.
Examples of intracrine peptide hormones: There are several protein/peptide hormones that are also intracrines. Notable examples that have been described in the references include:
The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors.
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. In humans, the major endocrine glands are the thyroid gland, parathyroid gland, pituitary gland, pineal gland, the testes (male), ovaries (female), and the adrenal glands. The hypothalamus, pancreas, and thymus also function as endocrine glands, among other functions. Other organs, such as the kidneys, also have roles within the endocrine system by secreting certain hormones. The study of the endocrine system and its disorders is known as endocrinology.
A hormone is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required for the correct development of animals, plants and fungi. Due to the broad definition of a hormone, numerous kinds of molecules can be classified as hormones. Among the substances that can be considered hormones, are eicosanoids, steroids, amino acid derivatives, protein or peptides, and gases.
Peptide hormones are hormones whose molecules are peptide. Peptide hormones have shorter amino acid chain lengths than protein hormones. These hormones have an effect on the endocrine system of animals, including humans. Most hormones can be classified as either amino acid–based hormones or steroid hormones. The former are water-soluble and act on the surface of target cells via second messengers; the latter, being lipid-soluble, move through the plasma membranes of target cells to act within their nuclei.
The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is also a secondary site of androgen synthesis.
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides are a family of hormone/paracrine factors that are structurally related. The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.
Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells. However, it also has normal functions in bone, teeth, vascular tissues and other tissues.
A hormone receptor is a receptor molecule that binds to a specific chemical messenger. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ligands, such as fatty acids and prostaglandins. Hormone receptors are of mainly two classes. Receptors for peptide hormones tend to be cell surface receptors built into the plasma membrane of cells and are thus referred to as trans membrane receptors. An example of this is Actrapid. Receptors for steroid hormones are usually found within the protoplasm and are referred to as intracellular or nuclear receptors, such as testosterone. Upon hormone binding, the receptor can initiate multiple signaling pathways, which ultimately leads to changes in the behavior of the target cells.
Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling.
Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.
In biology, cell signaling or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals. Cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports, or even from cell damage.
Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).
B))
Neuroendocrine differentiation is a term primarily used in relation to prostate cancers that display a significant neuroendocrine cell population on histopathological examination. These types of prostate cancer comprise true neuroendocrine cancers, such as small cell carcinoma, carcinoid and carcinoid-like tumors, as well as prostatic adenocarcinoma exhibiting focal neuroendocrine phenotype.