Pituitary glands

The pituitary gland plays a very important role in the overall control of the endocrine system. 

Pharmacology for the Health Care Professions Christine M. Thorp 2008 John Wiley Sons, Ltd 

ADH is secreted in response to an increase in plasma sodium chloride concentration or a decrease in circulating blood volume. ADH acts on kidney collecting duct cells to increase water reabsorption. In this way plasma sodium chloride concentration and/or blood volume are restored to normal. ADH also acts as a vasoconstrictor, which helps to maintain blood pressure if circulating blood volume has fallen. 

Lack of ADH causes diabetes insipidus, which is characterized by the production of large volumes of dilute urine. It is treated by replacement therapy with ADH or an analogue, desmopressin. 

Oxytocin is secreted in response to cervical dilation and uterine contractions during labour. By a positive feedback mechanism, oxytocin brings about further contraction of the utems until parturition is complete. Oxytocin is used clinically to induce or augment labour. 

As its name implies, the neurohypophysis is derived embryonically from nervous tissue. It is essentially an outgrowth of the hypothalamus and is composed of bundles of axons, or neural tracts, of neurosecretory cells originating in two hypothalamic nuclei. These neurons are referred to as neurosecretory cells because they generate action potentials as well as synthesize hormones. The cell bodies of the neurosecretory cells in the supraoptic nuclei produce primarily antidiuretic hormone (ADH) and the cell bodies of the paraventricular nuclei produce primarily oxytocin. These hormones are then transported down the axons to the neurohypophysis and stored in membrane-bound vesicles in the neuron terminals. Much like neurotransmitters, the hormones are released in response to the arrival of action potentials at the neuron terminal. 

The adenohypophysis is derived embryonically from glandular tissue, specifically, Rathke s pouch. This tissue originates from the oropharynx, or the roof of the mouth. It then migrates toward the embryonic nervous tissue destined to form the neurohypophysis. When these two tissues come into contact, Rathke s pouch loses its connection with the roof of the mouth and the pituitary gland is formed. Unlike the neurohypophysis, which releases hormones originally synthesized in the hypothalamus, the adenohypophysis synthesizes its own hormones in specialized groups of cells. Similar to the neurohypophysis, however, the release of these hormones into the blood is regulated by the hypothalamus. 

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In the anterior pituitary gland (see Hormones, anteriorpituitaryhormones), both adrenocorticotropic hormones (ACTH) and the endogenous opiate hormone, P-endorphin, are synthesized from a common prohormone (2) (see Opioids,endogenous). In the adrenal medulla, five to seven copies of another opiate hormone, methionine—enkephalin (Met-enkephalin), and one copy of leucine—enkephalin (Leu-enkephalin) are synthesized from each precursor molecule (3). 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

It was known as early as the 1920s that the pituitary gland contained a factor that could promote growth, but not until 1956 (1) was the factor isolated. hGH is extremely abundant in the pituitary, representing as much as 10% of this gland s dry weight, or 8 mg of hormone per gland (2). 

Natural Product hGH. In 1944 the preparation of a highly purified growth hormone from bovine pituitary glands was reported (37). Subsequendy, growth hormones derived from animal pituitaries were found to be ineffective in humans the existence of specificity among species for growth hormone was thus estabUshed. 

Extraction of hGH from pituitary glands has been accompHshed by a variety of procedures with or without protease inhibitors. One of the first commercial procedures used glacial acetic acid at 70°C to extract the hGH from the glands (39). 

The adrenal glands and pituitary glands have the highest tissue concentration of ascorbic acid. The brain, Hver, and spleen, however, represent the largest contribution to the body pool. Plasma and leukocyte ascorbic acid levels decrease with increasing age (152). Elderly people require higher ascorbic acid intakes than children to reach the same plasma and tissue concentration (153). 

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

It has been found that the growth hormone can be obtained in crystalline form from human pituitary glands by procedures comprising (1) extraction of the fresh glands with acetone, (2) extraction of the acetone residue with aqueous salt solutions, (3) precipitation from aqueous salt solutions by the addition of suitable miscible organic solvents of alkaline and acid pH, and finally crystallization from aqueous salt solutions by the addition of suitable miscible organic solvents. 

A disulfide bond between cysteine residues in different peptide chains links the otherwise separate chains together, while a disulfide bond between cysteine residues in the same chain forms a loop. Such is the case, for instance, with vasopressin, an antidiuretic hormone found in the pituitary gland. Note that the C-terminal end of vasopressin occurs as the primary amide, -CONHz, rather than as the free acid. 

Oxytocin, a nonapeptide hormone secreted by the pituitary gland, functions by stimulating uterine contraction and lactation during childbirth. Its sequence was determined from the following evidence ... 

Brain structure below the thalamus and main portion of the ventral region of the diencephalon, controlling homeostatic and nonhomeostatic basic body and brain functions, including circadian and feeding rhythms, energy metabolism, thermogenesis, sympathoadrenal, and neuroendocrine outflow (secretion of hormones by the pituitary gland), behavioral state and memory functions. 

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