Human physiology part 6
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Transcript of Human physiology part 6
Principles of Hormonal Control Systems (Part 6)
Chapter 10 John Paul L. Oliveros, MD, DPPS
Summary of Hormones
Hormone structure and synthesis
3 chemical classes of hormones Amines Peptides and proteins steroids
Amine Hormones Derivatives of
tyrosine Include:
▪ Thyroid hormones▪ Epinephrine▪ Norepinephrine▪ dompamine
Thyroid Hormones Thyroxine (T4) and
Triiodothyronine▪ Secreted by thyroid follicles
Iodine▪ Essential element of thyroid
hormones▪ Food GI tract blood
(converted to iodide) thyroid follicular cells (conversion back to iodine) thyroglobulin (incorportation with tyrosine and thyroglobulin precursor)
Thyroglobulin▪ Found in central spaces between
thyroid follicles▪ Endocytosis into follicular cells
and digested by lysosymes to release thyroid hormones
Thyroid Hormones
Thyroxine (T4) Secreted in large amounts Converted into T3 by most
tissue by deiodination Has no action unless converted
to T3 Persons with defective
deiodination enzyme manifest as thyroid hormone deficiencyeven with normal or increased T4
Triiodothyroxine (T3) More active than T4
Function: Regulation of O2 consumption Growth Brain development and function
Adrenal Medulla Glands and Dopamine
Adrenal gland Adrenal cortex Adrenal medulla▪ Modified sympathetic
ganglion▪ Axons release
secretions into blood (endocrine)
▪ Secrete 2 amine hormones▪ Epinephrine (E)
Secreted 4x more than NE
▪ Norepinephrine (NE)
Dopamine Secreted by cells in
the hypothalamus Function as a
hormone Also secreted by
small amounts in the adrenal glands
Peptide Hormones
Composes majority of hormones
preprohormones (ribosomes) prohormones (endoplasmic reticulum) hormones + peptides (golgi apparatus)
Many also functions as neurotransmitters/ neuromodulators
Steroid Hormones
Produced by the adrenal cortex and gonads, placenta
Cholesterol Steroid produced on a
particular cell depends on the types and concentration of enzymes present
Highly soluble Steroid producing cell
plasma membrane interstital fluid blood binding with plasma proteins
Hormones of the adrenal cortex Aldosterone
Mineralocorticoid Salt (mineral) balance Kidney’s handling of Na+, K+, H+
ions Cortisol and Corticosterone
Glucocorticosteroid Metabolism of glucose and other
organic nutrients Facilitation of response to stress Regulation of immune system
Dehydroepiandrosterone (DHEAS) and Androstenedione Androgens
▪ Include testosterone (testes)▪ Other adrenal androgens function like
testosterone but less potent▪ Play important role in adult female
and both sexes during puberty
Hormones of the adrenal cortex 3 distinct layers of
adrenal cortex Zona glomerulosa▪ High enzyme
concentration to convert corticosterone to aldosterone
Zona fasciculata Zona reticularis▪ Secretes more androgen
and cortisol▪ If less enzyme for
conversion to cortisol, may produce masculinzation in females
Hormones of the Gonads
High concentrations of enzymes to lead to androstenedione
Testes Androstenedione
testosterone Ovaries
High concentrations of aromatase
Androgens estradiol Some ovarian cells
screte progesterone
Hormone transport in blood Concentration of free hormone is more physiologically
important than total concentration
Hormone Metabolism and Excretion
Liver and kidneys Major organs for hormone
excretion and metabolism Target cells
May metabolize cetain peptide hormones
Plasma/blood Rapid elimination of peptide
hormones and catecholamines Less rapid elimination of
protein bound hormones (thyroid and steroid hormones)
Metabolism may activate some hormones instead of inactivating them
Mechanisms of Hormone action Hormone
receptors Ability to respond
depends on the ability of receptors for a homrone on the target cell
Receptors▪ Catecholamines/
peptide hormones▪ Plasma membrane
receptors
▪ Steroid/thyroid hormones▪ Intracellular receptors
Hormone Receptors Permissiveness▪ Hormone A must be
present for the full strength of hormone B’s effect
Mechanisms of Hormone Action Effects of peptide
hormones and catecholamines Activated receptors directly
influence either of the folowing:▪ Ion channels that are part of
the receptor▪ Enzyme activity that is part of
the receptor▪ Acivity of JAK kinases
associated with the receptor▪ G-proteins coupled in the
plasma membrane to effector proteins(ion channels and enzymes) that generate 2nd messengers
Mechanisms of Hormone Action Effect of steroids and
thyroid hormones Steroid hormones,
thyroid hormones, Vit D are closely related
Steroid hormone receptor superfamily
Binding of hormone with receptor causes activation/inhibition of particluar gene change in rate of protein synthesis coded by genes
Inputs that control Hormone Secretion
Most are released in short burst
Some are release in cycles
Controlled mainly by Changes in plasma
concentration of ions and nutrients
Neurotransmitters released from impinging neurons
Another hormone acting on the endocrine cell
In most cases, hormone secretion is influenced by more than 1 input
Inputs that control Hormone Secretion
Control by plasma concentrations of mineral ions or organic nutrients Major function of
hormone is to regulate (negative feedback) the plasma ion or nutrient controlling its secretion
Inputs that control Hormone Secretion
Control by neurons Adrenal medulla
behaves like a sypathetic ganglion
Other endocrine glands controlled by autonomic nervous system
Examples:▪ Insulin▪ Other gastrointestinal
hormones
Inputs that control Hormone Secretion
Control by other hormones Secretion of a
particular hormone is directly controlled by the blood concentration of another hormone
Trophic hormone▪ A hormone that
stimulates the secretion of another hormone
▪ Usually stimulate growth of the stimulated gland
Control Systems Involving the Hypothalamus and Pituitary
Pituitary gland Anterior pituitary▪ AKA adenohypophysis▪ With hypothalamo-pituitary
portal vessels▪ Local route for blood flow
directly from hypothalamus to anterior pituitary
Posterior pituitary▪ AKA neurohypophysis▪ Outgrowth of the
hypothalamus▪ Neural tissue▪ Axons that end near posterior
pituitary from hypothalamic nucleus▪ Supraoptic nuclei▪ Paraventricular nuclei
Posterior Hypothalamus
Hormones secreted are synthesized in the hypothalamus
Hormones travel to posterior pituitary enclosed in small vesicles
Stimuli (hormones/neurotransmitter) action potentials axon terminals exocytosis of hormones
2 posterior pitutary hormones Oxytocin▪ Acts on smooth
muscles in breast and uterus
Vasopressin▪ AKA anti-diuretic
hormone▪ Control of water
excretion by the kidneys
▪ Control of blood pressure
The hypothalamus and anterior pituitary
Hypophysiotropic hormones AKA hypothalamic
releasing hormones Hormones from the
hypothalamus that influence the anterior pituitary
1st of the 3 hormone sequence▪ Hypophysiotropic
hormone▪ Anterior pituitary hormone▪ Endocrine gland hormone
Anterior Pituitary Hormones Anterior pituitary secretes 8
hormones Only 6 functional/classical
hormones Follicle-Stimulating Hormone (FSH) Luteinizing Hormone (LH) Growth Hormoe (GH) Thyroid stimulating hormone
(TSH/thyrotropin) Prolactin Adrenocorticotropic hormone
(ACTH/corticotropin) Gonadotropic hormones
FSH LH
2 peptide hormones with unknown functions B-lipotropin B-endorphin
Hypophysiotropic Hormones Hypothalamic hormones that
regulate secretion of anterior pituitary hormones
Axons that secrete these hormones terminate in the median eminence around the hypothalamo-pituitary portal vessels
Difference with posterior pituitary hormone Neurons remain at the
hypothalamus, ending at its median eminence
Hypophysiotropic hormones enter median eminence capillaries hypothalamo-pituitary portal vessels anterior pituitary hormone▪ Anterior pituitary exposed to high
concentrations of hypophysiotrophic hormones
Hypophysiotrophic hormones
Hypophysiotrophic Hormones
Hypophysiotropic Hormones Neural control
Hypothalamus receive synaptic input from virtually all areas of the CNS
Large number of neurotransmitters are relased on synapses of hormone secreting hypothalamic neurons
Secretion of hypophysiotropic hormones can be influenced by drugs that influence neurotransmitters
Hypophysiotropic Hormones Hormonal Control of the
hypothalamus and anterior pituitary Negative feedback
(prominent feature of each sequence)
Effectivein dampening hormonal response / limiting extremes of hormonal secretory rates
Maintain plasma concentrations of the final hormone in a sequence constant whenever a disease-induced primary change occurs in the secretion or metabolism of the hormone
Hypophysiotropic Hormones Long-loop negative
feedback 3rd endocrine gland exerts
negative feedback effect on the hypothalamus/anterior pituitary gland
Exists on each of the 5 three-hormone sequences initiated by a hypophysiotropic hormone
Short-loop negative feedback influence of an anterior
pituitary hormone on the hypothalamus
Role of “nonsequence” hormones on hypothalamus/anterior pituitary
Hormone that is not itself in a particular sequence influences hypothalamus and anterior hormone secretion
e.g. Estrogen enhances secretion of prolactin
Candidate Hormones
Suspected hormones in humans butare not considered as classical hormones because Functions have not been
conclusively documented Have well documented
function in as paracrine/autocrine agent
Not certain if they reach target cell via blood
Melatonin▪ Produced by the pineal
gland▪ Probably important in the
setting of the body’s circadian rythms and sleep
▪ Ability to reduce jetlag▪ Relationship to seasonal
affective disorder (“winter depression”)
▪ Potentials:▪ Natural sleeping pill▪ Scavenge free radicals▪ Control of the reproductive
system
Endocrine Disorders
Types: Hyposecretion▪ Too little hormone
Hypersecretion▪ Too much hormone
Hyporesponsiveness▪ Reduced response of
target cells Hyperresponsivenes
s▪ Increase response of
target cells
Hyposecretion Primary hyposecretion▪ Gland is not able to
function normally▪ Examples:▪ Decrease cortisol due to
genetic absence of a steroid -forming enzyme in adrenal cortex
▪ Decrease thyroid hormones due to dietary deficiency of iodine
▪ Damage of an ndocrine gland due to: Infection Toxic chemicals
Endocrine Disorders
Hyposecretion Secondary hyposecretion▪ Gland secreting too little
hormonebecause there is not enough tropic hormone
▪ Example:▪ Decreased TSH (ant.
Pituitary) decreased thyroid hormone
Tertiary Hyposecretion▪ Decreased hormone
secretion from hypothalamus▪ Example:▪ Dec TRH dec TSH dec
thyroid hormones
Hyposecretion: Diagnosis▪ Determine concentration of a
hormone in the plasma or urine▪ Measure concentration of a
tropic hormone to distinguish between primary and secondary hyposecretion
▪ Administering tropic hormone or substance known to elicit secretion of a hormone▪ Primary defect: less than
normalincrease in hormone▪ Secondary defect: normal
increase in hormone
Treatment▪ Administering missing or
deficient hormone
Endocrine Disorders
Hypersecretion Primary hypersecretion
▪ Gland secreting too much of the hormone on its own
▪ Most common cause:▪ Hormone-secreting
endocrine cell tumor
Secondary hypersecretion▪ Excessive stimulation of a
gland by its tropic hormone
Tertiary hypersecretion▪ Hypersecretion of a
hypophysiotropic hormone (hypothalamus)
Hypersecretion Diagnosis
▪ Measure concentration of a hormone and its tropic hormone (blood/urine)
▪ Secondary hypersecretion▪ Concentration of both hormone and
topic hormone elevated
▪ Primary hypersecretion▪ Decreased secretion of a tropic
hormone because of negative feddback
▪ Tertiary hypersecretion▪ Increase in hypophysiotropic hormone
Treatment▪ Surgical removal or radiation
destruction of a endocrine tumor▪ Inhibitory drugs on hormon’s
synthesis▪ Drugs that block hormone’s effect on
target cells
Endocrine Disorders
Hyporesponsiveness Target cells do not
respondnormally to a hormone Types
▪ Deficiency of receptors for the hormone
▪ Events after hormone binding is defective
▪ Lack or deficiency of enzymes that catalyzes activation of a hormone
Diagnosis:▪ Plasma concentration of hormones
are normal or elevated despite diminished response of target cells
Examples▪ Diabetes mellitus (sugar diabetes)▪ Target cells are hyporesponsive to
insulin
Hyperresponsiveness Thyroid hormone cause up-
regulation of certain receptors of epinephrine▪ Tachycardia in hyperthyroidism
The End