ADH Secretion and its Effects on the Body

Hypothalamus and Pituitary Gland

• The pituitary gland's secretion is controlled by hormonal (anterior pituitary) or nervous (posterior pituitary) signals that originate in the hypothalamus.
• The hypothalamus receives data from multiple sources within the nervous system.
• It monitors the concentrations of nutrients, electrolytes, water, and hormones.

Endocrine Signaling

• An endocrine cell emits a chemical signal, or hormone, which acts as a first messenger.
• This messenger diffuses into the blood/ECF and travels to more or less distant target tissues equipped with specific receptors.

Hormones

• Hormones are chemical substances and signaling molecules that are produced and secreted by specific cells.
• Blood transports hormones (10–6 – 10–12 M) to target structures.
• Target cells have specific receptors for hormones.
• Hormones (H) trigger a specific response in distant target tissue.

Chemical Nature of Hormones

Steroid Hormones

• Steroid hormones come from cholesterol and are lipid-soluble.
• Examples include hormones of the adrenal cortex(glucocorticoids and mineralocorticoids), testes(testosterone), ovaries(estrogen, progesterone), placenta(estrogen progesterone), and vitamin D.

Amine Hormones

• Amine hormones are tyrosine derivatives.
• Hormones of the thyroid gland (lipid-soluble) and hormones of the adrenal medulla (water-soluble) are amine hormones.

Peptides and Proteins

• All remaining hormones are peptides and proteins and are water-soluble.

Hormone Synthesis

Steroid Hormones

• Steroid hormones are synthesized from cholesterol in the smooth endoplasmic reticulum and cytoplasm and mitochondria.

Thyroid Hormones

• Thyroid hormones are produced via enzymes in the cytoplasm.
• They are incorporated into thyroglobulin, stored in colloid within follicles outside the cell and bound to said thyroglobulin.

Catecholamines

• Catecholamines form in the cytoplasm via enzymes.
• They are stored in vesicles and released via exocytosis.

Polypeptides and Proteins

• Polypeptides/proteins are formed in the Endoplasmic Reticulum.
• They are also stored in vesicles and released via exocytosis.

Hormone Solubility and Transportation

• Water-soluble hormones are transported in free form, while lipid-soluble hormones are bound to plasma proteins.
• Water-soluble hormones bind to membrane receptors.
• Lipid-soluble hormones bind to cytoplasmic/nuclear receptors.
• Water-soluble hormones has a fast onset and short duration of action.
• Lipid-soluble hormones have a slower onset with a longer duration of action.

Hypothalamus-Pituitary Gland System

Hypohysis

• The hypohysis is another name for the pituitary gland.
• It's a small gland (~1 cm, ~0.5 g) located at the base of the brain below the hypothalamus, in the sella turcica.
• The pituitary stalk connects it to the hypothalamus.
• It includes the anterior lobe, posterior lobe, and pars intermedia.

Anterior Pituitary

• Also known as the adenohypophysis.
• It connects to the hypothalamus via vessels that make up the hypothalamic-hypophysial portal system
• Derives from Rathke's pouch.
• It contains granular epithelial cells that contain hormones and release hormones via exocytosis.

Posterior Pituitary

• The posterior pituitary is called the neurohypophysis
• It is an evagination of the third ventricle
• Glial-like cells known as pituicytes form there
  • Nerve endings of hypothalamic neurons, specifically from the supraoptic and paraventricular nucleus, are located here.

Posterior Pituitary Hormones

• The posterior pituitary releases oxytocin and antidiuretic hormone (ADH), also known as vasopressin.
• These hormones are synthesized in hypothalamic nuclei cell bodies (magnocellular cells, ER, Golgi apparatus).
• The supraoptic nucleus primarily synthesizes ADH.
• The paraventricular nucleus primarily synthesizes oxytocin.
• Neurophysins carry these hormones to nerve terminals.
• Vesicles store hormones in nerve terminals, and exocytosis (Ca2+) releases hormones into the blood due to nerve impulses from the hypothalamus.

ADH (Vasopressin)

General information

• ADH is a nanopeptide of 9 amino acids.
• V1A, V1B, and V2 are receptors for ADH.
• The metabolism of ADH includes rapid inactivation in the liver and kidney, with a short half-life of about 18 minutes.

Functions of ADH

• ADH has an antidiuretic effect, specifically in the kidney (V2 receptor).
• Vasoconstriction occurs due to ADH, in vessels and the kidneys(V1A receptor).
• ADH increases the secretion of ACTH in the anterior pituitary (V1B receptor).

Antidiuretic Effect

• Water reabsorption is stimulated by ADH in the distal nephron.
• V2 receptors increase the concentration of cAMP in tubular cells, which creates protein water channels that connect with the luminal membrane.
  • This increases both the number of water channels and the permeability of the luminal membrane for water.

Pressor Effect

• A decrease in blood pressure in the hypothalamus increases ADH secretion, which causes vasoconstriction in the kidney.
• This increases ECF volume, venous return, and cardiac output, ultimately increasing blood pressure.

Regulation of ADH Production

Osmoreceptors

• Specialized neuronal cells in the anterior hypothalamus (outside of the blood-brain barrier, called organum vasculosum of lamina terminalis) regulate ADH Production.
• Increased plasma osmolality leads to increased production of impulses (AP), which increases ADH secretion.
• Plasma osmolality under physiological conditions is 285 ± 10 mmol/kg.

Baroreceptors

• Decreases in blood pressure, and extracellular fluid volume increases ADH secretion.
• These events are registered by baroreceptors (in the high-pressure part of circulation) and volumoreceptors (low-pressure).
• The baroreceptors and volumoreceptors then stimulate hypothalamic neurons.

Other Stimuli

• Pain, nausea, and emotions increase ADH production.
• Nicotine, morphine, and angiotensin II increase ADH production
• Alcohol decreases ADH production.

Disorders of ADH Secretion

Hypersecretion

• Syndrome of inappropriate antidiuretic hormone secretion due to lung cancer or brain disease (SIADH).
• This causes an increase in ECF volume. It also leads to hyponatremia due to dilution of ECF and loss of salt in urine due to decreased salt reabsorption in the kidney.

Hyposecretion

• Diabetes insipidus is caused by lack of ADH production in the hypothalamus or defective V2 receptors.
• Consequences include polyuria with excessive excretion of diluted urine, and polydipsia, with the compensatory excessive drinking of water.
• Decreased water intake can lead to serious (lethal) dehydration.

Oxytocin

• Oxytocin is a peptide (9 AA) and its receptor is associated with activation, PLC → IP3→ Ca2+.
• Target organs are breasts and uterus.

Uterus and Oxytocin

• Oxytocin causes contraction of the uterus during late pregnancy and parturition.
• During this stage, there is increased expression of oxytocin receptors, thus increasing oxytocin secretion, and a changing estrogen/progesterone ratio.

Positive Feedback Mechanism

• The descent of the fetus through the birth canal causes stimulation (stretching) of the cervix.
• The sensory afferent fibers then signal hypothalamic nuclei to synthesize and secrete oxytocin by the posterior pituitary.
• This secretion then stimulates the contraction of the uterus and continued cervical stimulation by the fetus.

Breasts and Oxytocin

• Myoepithelial cells on the outside of alveoli contract, leading to milk ejection from alveoli to ducts.
• Stimulation of the nipple leads to a neuroendocrine reflex.
• Somatosensory tracts relay the message to hypothalamic nuclei, which causes a synthesis and release of oxytocin by the posterior pituitary.

Other Information

• Oxytocin is sometimes referred to as the “Love Hormone."
• Secretion of oxytocin occurs with touch, petting, and emotions, and is linked to sexual arousal, orgasm, and facilitation of sperm transport in the female genital tract.
• Oxytocin mediates maternal behavior and social behavior, including trust, empathy, positive relationships, communication, and faithfulness.

Anterior Pituitary Hormones

• The anterior pituitary has five types of secretory cells.
• Somatotropes secrete growth hormone (GH), which goes to peripheral glands.
• Corticotropes secrete adrenocorticotropin (ACTH), which goes to peripheral glands.
• Gonadotropes secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which goes to peripheral glands.
• Thyrotropes secrete thyroid-stimulating hormone (TSH), which goes to peripheral glands.
• Lactotropes secrete prolactin (PRL), which goes to mammary glands.
• FSH, LH, and TSH (and hCG) are proteins or glycoproteins and have a two-unit structure
• They contain an identical α-subunit and a unique β-subunit.

Anterior Pituitary Gland

• The hypothalamic-hypophysial portal system connects the hypothalamus and the anterior pituitary gland.
• Hypothalamic neurons produce hormones in various parts of the hypothalamus.
• The neurons then secrete the hormones at the median eminence, regulating anterior pituitary secretion.
• This secretion includes releasing and inhibitory hormones.

Anterior Pituitary Regulation

Releasing Hormones

• Releasing hormones act on the anterior pituitary gland triggering the release of hormones
  • Examples include: Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH), Growth hormone-releasing hormone (GHRH), and Gonadotropin-releasing hormone (GnRH)

Inhibitory Hormones

• Inhibitory Hormones inhibits release of hormones
• Growth hormone inhibitory hormone (GHIH, somatostatin)
• Prolactin inhibitory hormone (dopamine)

Growth Hormone

General Information

• Growth hormone (GH) is a polypeptide synthesized by somatotropes (acidophils).
• GH is protein-bound and free in plasma, undergoing rapid degradation in the liver.
• GH binds membrane receptors, triggering cascades via, PLC-PKC (phospholipase C → proteinkinase C), JAK2-Stat (tyrosinkinases → signal transducers and activators of transcription, and MAPK (tyrosinkinases → ras proteins → mitogen-activated kinases → production of transcription factors).

Effects of Growth Hormones

• Growth hormone has metabolic and growth related effects
• GH directly has metabolic effect where growth effects depend on somatomedins (cells growth, stimulation of mitosis, differentiation, maturation of cells), induces growth of all tissues that are able of growth.

Metabolic Effects

• Growth hormone increases protein synthesis by increasing amino acid transport across the cell membrane, increasing transcription of DNA to RNA, and increasing protein synthesis by ribosomes.
• It decreases the catabolism of proteins and AA and promotes mobilization of fatty acids (FA) from adipose tissue.
• Ketogenic effect (acetoacetic acid ⟵ FA in the liver)

Glucose Metabolism

• Glucose uptake (muscles, fat) decreases and glucose production by the liver increases upon administration of growth hormones.
• It includes a diabetogenic effect of growth hormone: increased plasmatic glucose leads to increased insulin secretion, which leads to insulin resistance of target tissues and the exhaustion of B-cells, which leads to diabetes mellitus

Growth Effects of GH

• The growth effects of growth hormones are mediated by somatomedins (insulin-like Growth Factors (IGFs)) and are polypeptides.
• The liver produces growth factors following growth hormones stimulating cartilage.
• Growth hormone and somatomedins' effects are inseparable and complement and mediate each other.
• Most importantly somatomedin C = IGF-I

IGF-I (Somatomedin C)

• Independent of GH before birth.
• After birth, secretion is stimulated by GH and increases in childhood, peaks in puberty, and decreases with age.

IGF-II

• Less affected by GH.
• Important for growth during fetal development.

Somatomedins

• Protein deposition ↑ growth in almost all tissues (mainly the skeletal frame).
• Cartilage Growth occurs as GH converts stem cells into cells sensitive to cartilage growth stimulated by IGF-I.
• The growth of bone in childhood before the closure of growth plates includes increased deposition of proteins in osteogenic cells, the reproduction rate of osteogenic cells, and conversion of chondrocytes into osteogenic cells.

Growth Periods

• Growth involves genes, nutrition, hormones (GH, insulin, T, sex hormones, and glucocorticoids).
• Fetal growth occurs due to IGF-II, insulin, and T-hormones.
• The first growth period is a continuation of fetal growth.
• The second growth period involves puberty and the termination of growth by estrogen.

Regulation of GH Secretion

• Growth hormone secretion is pulsatile and regulated by the hypothalamus with growth hormone-releasing hormone and somatostatin (GHIH).
• Negative feedback occurs when GH increases IGF-1 in plasma.
• High levels of IGF-1stimulates somatostatin secretion.
• Somatostatin secretion decreases levels of growth hormone-releasing hormone and growth hormone.

Growth Hormone Secretion

• Factors that increase GH secretion include energy deficiency or starvation, protein deficiency, traumatic events, the presence of testosterone and estrogen and deep sleep.
• Factors taht decrease GH secretion include high glucose and fatty acid levels, obesity, aging, release of INGF1, GHIH and REM sleep.

Hormones of Pars Intermedia

• Proopiomelanocortin (POMC) is the precursor molecule.
• In the anterior pituitary it becomes ACTH and β-endorphin.
• In the pars intermedia it becomes β-endorphin, α- and β-MSH.
• MSH is triggers melanin formation and hyperpigmentation due to ACTH is often linked to hypersecretion.

Pituitary Insufficiency

Panhypopituitarism

• A condition involving ↓ secretion of all pituitary hormones.
• Can be congenital or acquired
• In childhood, this results in Dwarfism linked to normal physical proportions x ↓ rate of development
• In adulthood, conditions includes tumors, thrombosis, and insufficient secretion of sex hormone.
• Both children and adults encounter lethargy, weight gain, and sex dysfunctions.

Pituitary Hyperfunction

General Information

• This condition refers to a case of excessive release of pituitary hormones
• Can lead to tumors from corticotropes → and ACTH hyperproduction or from somatotropes → GH hyperproduction.

Gigantism

• Childhood hypersecretion before fusion of epiphysis with diaphysis that results in abnormal body height (cca 250 cm), as well as very rapid All tissues and bone growth.
• Common occurence of Hyperglycemia → diabetes mellitus

Acromegaly

• Adulthood Hypersecretion after fusion of epiphysis with diaphysis, leading to an increase in bone thickness, and growth of soft tissue
• Involves Hands, feet, cranium (nose, supraorbital ridges, lower jaw).
• Can manifest as Kyphosis, and/or Tendency to osteoarthritis and manifests due to a local tumour action leading to headache and impaired vision (pituitary grand close to optic chiasm)

Explore the effects of increased and decreased ADH secretion. This quiz covers the conditions resulting from ADH imbalances, like excessive urine excretion and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Also covers the hypophysial portal system, specialized neurons and hormone secretion.