Endocrine Glands: Secretion and Action of Hormones Chapter 11 Part 1 Endocrine Glands: Secretion and Action of Hormones

Classic Definition of a Hormone Hormone - Chemical messenger produced by a ductless gland or tissue and carried in the blood/lymph to a target organ where it effects a change in cellular activity. EffectorCell 1 TargetCell 2 Capillary

Endocrine Glands Testis in Male Adrenal Gland Hypothalamus Ovary Kidney Pituitary Located at base of brain Thyroid Parathyroid Testis in Male

Anterior & Posterior Pituitary Higher Centers of Brain Control All Hormonal Functions Cerebrum Hypothalamus Third Ventricle Pineal Body Medulla Oblongata Pituitary Stalk Anterior & Posterior Pituitary Cerebellum

Anatomy of Cow Brain Infundibular Stalk Diaphragma sellae Pituitary Spenoid Bone

Control of Endocrine Gland Function Hypothalamic-Pituitary Interrelationships Hypothalamus Secreting neurons: GnRH, CRH, TRH, GHRH Nerve cells which release peptide hormones: Oxytocin, ADH Superior Hypophyseal Artery Hypophyseal Portal Vessels Pituitary Stalk Posterior Pituitary: Neurohypophysis Nerve endings come directly from hypothalamus Anterior Pituitary Adenohypophysis non-neural tissue Release of LH, FSH, ACTH, PRL, GH, TSH Release of Oxytocin or ADH into circulation

Endocrine Glands and Hormones Secrete biologically active molecules into the blood. Lack ducts. Carry hormones to target cells that contain specific receptor proteins for that hormone. Target cells can respond in a specific fashion. Different from nervous system – Nervous system is fast, short-term reactions Endocrine – longer duration, adaptation response.

Endocrine Glands and Hormones (continued) Neurohormone: Specialized neurons that secrete chemicals into the blood rather than synaptic cleft. Chemical secreted is called neurohormone. Hormones: Affect metabolism of target organs. Help regulate total body metabolism, growth, and reproduction.

Other forms of endocrine action 1) Paracrine - released from effector cell (E) interact with a different target cell (T1). 2) Autocrine - secreted by E interact with original E cell or similar cell types. 3) Juxtacrine -expressed on surface of E and interacts with target cell (T2) via direct cell-cell contact. 4) Intracrine - is not secreted by E and interacts with an intercellular receptor. E E T

Ectocrine Flehmen Pheromones: A chemical substance that is liberated by one animal and causes a relatively specific behavior modification in a recipient animal following its chemoreception Lee-Boot effect: Crowded female mice become anestrous when no males are present. Bruce effect: A newly mated female mouse will abort if placed with a strange male (not the previous mate). Dormitory effect: menstrual synchrony in all-females living groups

Common Aspects of Neural and Endocrine Regulation APs are chemical events produced by diffusion of ions through neuron plasma membrane. Action of some hormones are accompanied by ion diffusion and electrical changes in the target cell. Nerve axon boutons release NTs. Some chemicals are secreted as hormones, and also are NTs. In order for either a NT or hormone to function in physiological regulation: Target cell must have specific receptor proteins. Combination of the regulatory molecule with its receptor proteins must cause a specific sequence of changes. There must be a mechanism to quickly turn off the action of a regulator.

Most hormones belong to one of 4 structural classes Peptides & Amines (E, NE % DA) are hyrophilic Steroids and eicosanoids are hydrophobic

Structural Classes Amines: Peptides, Polypeptides and Proteins Hormones derived from tyrosine and tryptophan. NE, Epi, T4. Peptides, Polypeptides and Proteins Polypeptides Chains of < 100 amino acids in length. ADH. Ex: Adrenalcorticotropic Hormone (ACTH) – 39 amino acids Peptide - Few - Several amino acids Ex: Gonadotropin Releasing Hormone (GnRH) - 10 amino acids Oxytocin - 8 amino acids Protein hormones: Polypeptide chains with > 100 amino acids. Growth hormone, Insulin, ACTH. Prolactin - 198 amino acids

Structural Classes Glycoprotein - Protein hormone with carbohydrate molecules Some have large amount of sialic acid – FSH Steroids Lipids derived from cholesterol Are lipophilic (fat loving; can diffuse through plasma membrane) hormones. Ex – testosterone, estradiol, progesteone, and cortisol

Effects of [Hormone] on Tissue Response [Hormone] in blood reflects the rate of secretion. Half-life: Time required for the blood [hormone] to be reduced to ½ reference level. Minutes to days. Normal tissue responses are produced only when [hormone] are present within physiological range. Varying [hormone] within normal, physiological range can affect the responsiveness of target cells.

Percent of Carbohydrate and Size of Protein Effects Half-Life in Blood Equine Chorionic Gonadotropin - 45% Carbohydrate eCG % in Blood After Injection Human Chorionic Gonadotropin - 30% Carbohydrate Follicle Stimulating Hormone 8% Carbohrydrate GnRH Oxytocin Luteinizing Hormone little sialic acid Time required to remove or clear half of the dose from the blood

Chemical Classification of Hormones (continued)

Δ4 Δ5 Δ5: Primates, Sheep, Cattle Δ4: Pigs, rats, mice (Conley and Bird 1997)

Hormone Synthesis Protein Hormones Synthesized at ribosomes as large precursor proteins Preprohomrone converted to prohormone within rough ER Golgi apparatus – packages prohormone and converts it to hormone Stored in secretory granules Upon stimulation – get exocytosis Requires: 1. ATP 2. Ca

The flow of genetic information in a typical cell

b a Anterior Pituitary Hormones Such as LH, FSH and TSH (Thyroid Stimulating Hormone) have Two Chains Alpha - a Beta - b b S S a a chain is identical between FSH, LH and TSH. b chain gives the hormone its specific action. Need both chains together for biological activity

        TSH FSH LH hCG mRNA Transcription Translation TSH, LH and FSH: Pituitary Glycoprotiens hCG: placental

Synthesis of Steroid Hormones Ex: glucocorticoids, mineralocorticoids, sex steroids Formed from cholesterol – which is used immediately or stored in cell Type of steroid hormone produced depends on presence of specific enzymes EX: adrenal cortex cell – contain enzymes needed for production of glucocorticoids or mineralocorticoids Steroid hormones secreted immediately from cell after formation Rate of steroid hormone secretion controlled by rate of production

Cholesterol C27 Pregnenolone C21 Androgens C19 Glucocorticoids C21 Mineralocorticoids, glucocorticoids and steroids are synthesized from cholesterol Cholesterol C27 Pregnenolone C21 Glucocorticoids C21 Mineralocorticoids C21 Androgens C19 Estrogens C18

Chemical Classification of Hormones (continued) Hormones can also be divided into: Polar: H20 soluble. Nonpolar (lipophilic): H20 insoluble. Can gain entry into target cells. Steroid hormones and T4. Pineal gland secretes melatonin: Has properties of both H20 soluble and lipophilic hormones.

Prohormones and Prehormones Precursor is a longer chained polypeptide that is cut and spliced together to make the hormone. Proinsulin. Preprohormone: Prohormone derived from larger precursor molecule. Preproinsulin. Prehormone: Molecules secreted by endocrine glands that are inactive until changed into hormones by target cells. T4 converted to T3.

Prohormones and Prehormones

Hormonal Interactions Synergistic: Two hormones work together to produce a result. Additive: Each hormone separately produces response, together at same concentrations stimulate even greater effect. NE and Epi. Complementary: Each hormone stimulates different step in the process. FSH and testosterone.

Hormonal Interactions (continued) Permissive effects: Hormone enhances the responsiveness of a target organ to second hormone. Increases the activity of a second hormone. Prior exposure of uterus to estrogen induces formation of receptors for progesterone. Antagonistic effects: Action of one hormone antagonizes the effects of another. Insulin and glucagon.

Effects of [Hormone] on Tissue Response (continued) Priming effect (upregulation): Increase number of receptors formed on target cells in response to particular hormone. Greater response by the target cell. Desensitization (downregulation): Prolonged exposure to high [polypeptide hormone]. Subsequent exposure to the same [hormone] produces less response. Decrease in number of receptors on target cells. Insulin in adipose cells. Type 2 diabetes Pulsatile secretion may prevent down regulation.

Mechanisms of Hormone Action Hormones of same chemical class have similar mechanisms of action. Similarities include: Location of cellular receptor proteins depends on the chemical nature of the hormone. Events that occur in the target cells. GH and Prolactin (Trophic hormones - increase in growth) To respond to a hormone: Target cell must have specific receptors for that hormone (specificity). Hormones exhibit: Affinity (bind to receptors with high bond strength). Saturation (low capacity of receptors).