Neurophysins

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Neurophysins are carrier proteins which transport the hormones oxytocin and vasopressin to the posterior pituitary from the paraventricular and supraoptic nucleus of the hypothalamus, respectively. Inside the neurosecretory granules, the analogous neurophysin I and II form stabilizing complexes via covalent interactions. [1] Stabilizing neurophysin-hormone complexes that are formed within neurosecretory granules located in the posterior pituitary gland aid in intra-axonal transport. [2] During intra-axonal transport, the neurophysin's are believed to prevent the bound hormone from leaking into the cytoplasmic space and proteolytic digestion via enzymes. [3] However, due to the low concentration of neurophysin in the blood, it is likely the protein-hormone complex dissociates, indicating the neurophysin does not aid in transporting the hormone through the circulatory system. [2]

Contents

Neurophysins are also secreted out of the posterior pituitary hypothalamus, each carrying their respective associated passenger hormone. When the posterior pituitary hypothalamus secretes vasopressin and its neurophysin carrier, it also secretes a glycopeptide.

There are two types:

Biosynthesis of Neurophysins

These proteins are synthesized in the cell bodies of the supraoptic and paraventricular regions of the hypothalamus.

The disulfide-rich neurophysin protein is suggested to be congruent with the synthesis of insulin in which a precursor molecule of higher molecular weight is proteolytically cleaved and forms disulfide linkages. [2]

Although not enough data has been obtained, it is hypothesized that there is a common precursor molecule between neurophysin and the two hormones it stabilizes. [2]

Structure

Neurophysins are acidic proteins with a molecular weight of approximately 10,000 Da that are rich in cysteine, glycine, and proline residues . The protein is double domain with a polypeptide chain of 93-95 residues with 14 cysteine residues forming 7 disulfide bridges . Domain I contains a COOH terminal with a disulfide loop; domain II lacks this COOH terminal disulfide loop . Based on the resemblance of the disulfide loop present on vasopressin and oxytocin, it is suggested that the hormones form covalent linkages to this disulfide loop present on the COOH terminal of domain I. [4]

Neurophysin II protein domain unbound to vasopressin PDB 1npo EBI.jpg
Neurophysin II protein domain unbound to vasopressin
Neurophysin-Oxytocin complex Oxytocin-neurophysin.png
Neurophysin-Oxytocin complex

See also

Related Research Articles

Pituitary gland Endocrine gland at the base of the brain

In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a pea and weighing 0.5 grams (0.018 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypophysis rests upon the hypophysial fossa of the sphenoid bone in the center of the middle cranial fossa and is surrounded by a small bony cavity covered by a dural fold. The anterior pituitary is a lobe of the gland that regulates several physiological processes. The intermediate lobe synthesizes and secretes melanocyte-stimulating hormone. The posterior pituitary is a lobe of the gland that is functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk.

Hypothalamus Area of the brain below the thalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

Vasopressin

Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon of that cell, which terminates in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

Oxytocin Peptide hormone and neuropeptide

Oxytocin (Oxt) is a peptide hormone and neuropeptide. It is normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to love and in labor. This helps with birth, bonding with the baby, and milk production.

Posterior pituitary Posterior lobe of the pituitary gland

The posterior pituitary is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary, and serve as a site for the secretion of neurohypophysial hormones directly into the blood. The hypothalamic–neurohypophyseal system is composed of the hypothalamus, posterior pituitary, and these axonal projections.

Supraoptic nucleus

The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 neurons.

Paraventricular nucleus of hypothalamus

The paraventricular nucleus is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

Magnocellular neurosecretory cells are large neuroendocrine cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the nucleus circularis. There are two types of magnocellular neurosecretory cells, oxytocin-producing cells and vasopressin-producing cells, but a small number can produce both hormones. These cells are neuroendocrine neurons, are electrically excitable, and generate action potentials in response to afferent stimulation.

A neurohormone is any hormone produced and released by neuroendocrine cells into the blood. By definition of being hormones, they are secreted into the circulation for systemic effect, but they can also have a role of neurotransmitter or other roles such as autocrine (self) or paracrine (local) messenger.

Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release message molecules (hormones) into the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration. An example of a neuroendocrine cell is a cell of the adrenal medulla, which releases adrenaline to the blood. The adrenal medullary cells are controlled by the sympathetic division of the autonomic nervous system. These cells are modified postganglionic neurons. Autonomic nerve fibers lead directly to them from the central nervous system. The adrenal medullary hormones are kept in vesicles much in the same way neurotransmitters are kept in neuronal vesicles. Hormonal effects can last up to ten times longer than those of neurotransmitters. Sympathetic nerve fiber impulses stimulate the release of adrenal medullary hormones. In this way the sympathetic division of the autonomic nervous system and the medullary secretions function together.

Neurophysin I is a carrier protein with a size of 10 KDa and contains 90 to 97 amino acids. It is a cleavage product of preprooxyphysin. It is a neurohypophysial hormone that is transported in vesicles with oxytocin, the other cleavage product, along axons, from magnocellular neurons of the hypothalamus to the posterior lobe of the pituitary. Although it is stored in neurosecretory granules with oxytocin and released with oxytocin, its biological action is unclear.

Pituitary stalk Anatomical structure

The pituitary stalk is the connection between the hypothalamus and the posterior pituitary. The floor of the third ventricle is prolonged downward as a funnel-shaped recess—the infundibular recess—into the infundibulum, where the apex of the pituitary is attached. It passes through the dura mater of the diaphragma sellae as it carries axons from the magnocellular neurosecretory cells of the hypothalamus down to the posterior pituitary where they release their neurohypophysial hormones, oxytocin and vasopressin, into the blood.

Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

Vasotocin

Vasotocin is an oligopeptide homologous to oxytocin and vasopressin found in all non-mammalian vertebrates and possibly in mammals during the fetal stage of development. Arginine vasotocin (AVT), a hormone produced by neurosecretory cells within the posterior pituitary gland (neurohypophysis) of the brain, is a major endocrine regulator of water balance and osmotic homoeostasis and is involved in social and sexual behavior in non-mammalian vertebrates. In mammals, it appears to have biological properties similar to those of oxytocin and vasopressin. It has been found to have effects on the regulation of REM sleep. Evidence for the existence of endogenous vasotocin in mammals is limited and no mammalian gene encoding vasotocin has been confirmed.

Herring bodies or neurosecretory bodies are structures found in the posterior pituitary. They represent the terminal end of the axons from the hypothalamus, and hormones are temporarily stored in these locations. They are neurosecretory terminals.

Neurophysin II

Neurophysin II is a carrier protein with a size of 19,687.3 Da and is made up of a dimer of two virtually identical chains of amino acids. Neurophysin II is a cleavage product of the prepro-vasopressin. It is a neurohypophysial hormone that is transported in vesicles with vasopressin, the other cleavage product, along axons, from magnocellular neurons of the hypothalamus to the posterior lobe of the pituitary. Although it is stored in neurosecretory granules with vasopressin and released with vasopressin into the bloodstream, its biological action is unclear. Neurophysin II is also known as a stimulator of prolactin secretion.

Parvocellular neurosecretory cells are small neurons within paraventricular nucleus (PVN) of the hypothalamus. The axons of the parvocellular neurosecretory cells of the PVN project to the median eminence, at the base of the brain, where their neurosecretory nerve terminals release peptides into blood vessels in the hypothalamo-pituitary portal system. The blood vessels carry the peptides to the anterior pituitary gland, where they regulate the secretion of hormones into the systemic circulation.

Neurohypophysial hormone

The neurohypophysial hormones form a family of structurally and functionally related peptide hormones. Their main representatives are oxytocin and vasopressin. They are named after the location of their release into the blood, the neurohypophysis.

Howard Sachs (scientist)

Howard Sachs, was a biochemist who helped pioneer the study of neuroendocrinology. His discoveries concerning the production of the hormone vasopressin laid the foundation for the field of hormone biosynthesis.

References

  1. Airaodion AI, Ekenjoku JA, Ogbuagu EO, Okoroukwu VN, Ogbuagu U (2019-10-22). "Carica papaya Leaves Might Cause Miscarriage". Asian Research Journal of Gynaecology and Obstetrics: 1–9.
  2. 1 2 3 4 Breslow E (June 1979). "Chemistry and biology of the neurophysins". Annual Review of Biochemistry. 48 (1): 251–74. doi:10.1146/annurev.bi.48.070179.001343. PMID   382985.
  3. Breslow E (June 1979). "Chemistry and biology of the neurophysins". Annual Review of Biochemistry. 48 (1): 251–74. doi:10.1146/annurev.bi.48.070179.001343. PMID   382985.
  4. Drenth J (March 1981). "The structure of neurophysin". The Journal of Biological Chemistry. 256 (6): 2601–2. PMID   7204368.