Jan 6 - Endocrinology and Metabolism Flashcards
What does the endocrine system control?
Development and growth
Energy regulation (storage and mobilization)
Internal homeostasis (fluids, ions)
Reproduction (sex, pregnancy, lactation)
What is the difference between endocrine, paracrine and autocrine?
Endocrine hormones is borne via the bloodstream
Paracrine hormones act in a local environment
Autocrine hormones act on the secreting cell
What is the pituitary gland?
Probably the most important hormone producing organ (size of a chickpea). It produces some of the most important hormones
Name the different chemical classes of hormones
Amino hormones (derived from tyrosine) Peptide and protein hormones (encoded in genes, i.e. insulin) Steroid hormones (derived from cholesterol)
Describe amino hormones
Derived from the amino acid tyrosine
Includes the catecholamines epinephrine and norepinephrine from adrenal medulla
Includes thryoid hormones thryroxine (T4) and trioiodothyronine (T3) and thryoid
Describe protein and polypeptide hormones
They are transcribed from genes.
They are translated in rough ER, processed in Golgi, stored in secretory vesicles.
May undergo one or more post-translational modifications including cleavage, glycosylation, disulfide bridging.
Explain how protein and polypeptide hormones exit the cells
They are stored in secretory granules and released on stimulation. It is a calcium ion dependant event (exocytosis). They cannot cross membrane freely as they are hydrophilic
Describe steroid hormones
Not encoded in genes, but derived from cholesterol through enzymatic reactions. They include glucocorticoids, mineralcorticoids, androgens, estrogens and progestins
How do steroid hormones enter the cell?
Steroids are lipophilic molecules that freely cross membranes. Steroids are not stored in endocrine glands but are released as made. Steroids travel in the blood associated with steroid-binding globulins (SBGs)
What are the three main axes (feedback loops) involving the hypothalamus and the pituitary control? What do they do?
The hypothalamic-pituitary-thyroid axis (HPT)
The hypothalamic-pituitary-adrenal axis (HPA)
The hypothalamic-pituitary-gonadal axis (HPG)
They control much of the endocrine system and they operate by negative feedback loops
Explain the HPG axis
GnRH secreted by the hypothalamus stimulates the secretion of FSH and LH in the pituitary. FSH/LH stimulates the secretion of estrogen and progesterone. Once the levels of estrogen/progesterone are high enough, they travel to the brain to inhibit the secretion of FSH/LH and GnRH
What is positive feedback control? Give two examples
It is less common, but used when amplification is needed. Example 1: the mid-cycle surge of gonadotropins (LH and FSH) stimulated by high levels of estrogens. Example 2: Oxytocin (made in the hypothalamus and released by the posterior pituitary) during parturition and suckling
Explain the activation of bioactive hormones. Give examples
It requires modifications after synthesis and release. Example 1: 5-alpha reductase converts testosterone (T) to bioactive dihydrotestosterone (DHT). Example 2: Aromatase converts testosterone of estrogen. Example 3: Thyroxine (T4) to triiodotyronine (T3, more active form thyroid hormone)
Explain endocrine rhythms
Hormone levels may fluctuate in response to internal (neurotropic) and external stimuli (food, light, activity). Circadian and longer rhythms also exist
What is the physiological and clinical significance of pulsatile hormone secretion
It maintains organ sensitivity, e.g. prevents down-regulation of receptors. Abolished pulsatile secretion results in diminished hormone secretion, e.g. GnRH agonist leads to clinical castration
What is the mechanism of hormone action?
All hormone action is receptor mediated. Hormone receptors act as allosteric effectors; hormone binding to specific receptor results in conformational change in receptor that conveys a signal to target cell
Describe cell surface receptors
Peptide hormones and catecholamines bind to cell surface receptors. Receptors have extracellular, transmembrane and intracellular domains. Extracellular domain contains ligand (hormone) binding site
Describe the steps in cell surface receptor binding
The hormone traveling in the blood stream with a binding protein detaches from the binding protein. It binds with the extracellular domain of the receptor. The intracellular domain of the receptor activates a second messenger system causing an altered cell function
What are second messengers?
They are released within the cell upon hormone binding to the extracellular domain of the receptor. They can include cAMP or cGMP, the phospholipids diacylglycerol (DAG) and inositol triphosphate (IP3), calcium, etc.
Describe the action of the second messenger cAMP
G-protein-coupled receptors activate adenylate cyclase via the alpha domain of the G-protein. Adenylate cyclase converts ATP into cAMP, which goes on to activate other proteins that alter cell function
Describe the action of phospholipids as second messengers
Phosphorylation of receptors activates phospholipase C. Phospholipase C converts PIP2 into DAG and IP3. DAG activates other enzymes and IP3 causes release of calcium. Further processing alters cell function
Describe the action of kinase receptors via the example of insulin
Insulin binds to the receptors, causing them to dimerise. Dimerised receptors undergoes transautophosphorylation. Linking protein binds to phosphate group. Linking protein activates second messanger systems
Describe receptor down-regulation
After hormone binding, receptors may be internalized (coated pits). Leads to reduced responsiveness of target cell (usually temporary). Receptor may be recycled to cell surface or degraded
Describe intracellular receptors
Steroid and thyroid hormones act via intracellular receptors. Hormone-receptor complex interacts directly with DNA at the promotor of specific genes
Describe the action of intracellular receptors
The steroid hormone diffuses through the cell membrane. The hormone binds to an intracellular receptor either the cytoplasm or the nucleus, forming a hormone-receptor complex. The complex interacts with DNA in the nucleus, altering gene expression and cell function
What causes endocrine dysfunction due to changes in hormone levels
It can arise from a variety of factors. Most commonly it results from abnormal plasma concentrations of a hormone caused by inappropriate rates of secretion
What is primary hyposecretion? What are the causes?
Too little hormone is secreted due to abnormality within the gland. Causes: genetic, dietary, chemical or toxic, immunologic, other disease processes such as cancer
What is secondary hypsecretion?
Gland is normal but too little hormone is secreted due to deficiency of tropic hormone
What is primary hypersecretion?
Too much hormone is secreted due to abnormality within gland (e.g. hormone secreting hormones)
What is secondary hypersecretion?
Excessive stimulation from outside the gland causes oversecretion
What are the two types of endocrine dysfunction at the target cells?
Receptor defects (mutations causing inactivity or constitutive activity, reduced/increased numbers, receptor agonist/antagonist) Post-receptor signal transduction defects (e.g., second messangers, coupling proteins)
