Endocrine

Homeostasis

• system of feedback responses to maintain a steady state

Negative feedback loop

• common control mechanisms

• responsiveness of target cells to hormonal action feeds back to control the inciting endocrine organ

• ex: blood osmolality regulation

  • increased blood osmolality → hypothalamic osmoreceptors stimulated → increased circulating vasopressin → increased water permeability of collecting duct of kidney → water reabsorbed from nascent urine → decreased blood osmolality

Positive feedback loop

• few examples, mostly seen in reproduction

Hypothalamus

• connects brain to endocrine organs

• controls thirst/appetite, body temperature, posterior and anterior secretion, defensive reactions, & body rhythms

• receives sensory input & translates to changes in endocrine function to maintain peripheral homeostasis

• neural connection to posterior pituitary, vascular portal connection to anterior pituitary

Anterior pituitary hormones

• FSH

• LH

• ACTH

• TSH

• prolactin

• GH

• controlled by releasing hormones

Posterior pituitary hormones

• ADH/vasopressin

• oxytocin

• secreted via neurosecretion from magnocellular neurons from supraoptic & paraventricular nuclei

Oxytocin

• secreted in response to mammary gland or cervical stimulation

• causes milk letdown, uterine contractions, & luteolysis

Vasopressin

• aka antidiuretic hormone

• 3 types of receptors

• increases BP & renal water resorption, concentrates urine, decreases osmolality of body fluids

Hypothalamic hypophysiotropic hormones

• releasing hormones: GnRH, CRH, TRH, PRH, GHRH

• highest concentration in hypophyseal portal blood

• released from median eminence of hypothalamus

• most affect secretion of more than 1 anterior pituitary hormone

Calcium regulation

• 3 hormones: PTH (most important), calcitonin, vitamin D

• 3 body systems: kidney, intestine, bone

Parathyroid gland

• chief cells, clear cells, & oxyphil cells

• PTH from chief cells

Parathyroid hormone

• increases blood calcium

• reduces blood phosphorus

• promotes bone remodeling

• activates vitamin D

• stimulated by hypocalcemia & hyperphosphatemia

• inhibited by hypercalcemia & vitamin D

Parathyroid hormone targets

• kidneys (increases calcium reabsorption & vitamin D synthesis, inhibits phosphate reabsorption)

• bone (increases resorption during hypocalcemia/activates osteoclasts via osteoblasts)

Calcitonin

• decreases blood calcium

• decreases bone loss/resorption, prevents excessive bone loss during lactation

• stimulated by hypercalcemia

• produced by parafollicular cells in the thyroid

• gastrin stimulates release in response to dietary calcium

Vitamin D

• increases calcium & phosphorus absorption & reabsorption

• modulates bone resorption and remodeling

• inhibits PTH via inhibition of chief cell proliferation

• regulates immune function

• D3 from animals, D2 from fungi/plants

PTHrP

• paracrine factor, mimics PTH

Thyroid gland

• regulates tissue/energy metabolism & cell differentiation

• secretion regulated by negative feedback

Thyroid negative feedback loop

• hypothalamus secretes TRH (TSH-releasing hormone)

• pituitary secretes TSH (thyroid stimulating hormone)

• thyroid secretes T3/T4

• T3/T4 inhibit release of TRH and TSH

Thyroid hormone functions

• increase metabolic activity

• necessary for fetal development & growth

• important in tissue differentiation & reproductive function

• targets every cell in the body via intracellular nuclear receptors

• modulates transcription

Thyroid hormone binding

• 99% of hormones bound to proteins (TBG, TTR, & albumin)

• avoids excessive action of free thyroid hormone on cells, prevents loss of hormones into urine, & protects hormones from being metabolized

Thyroid hormone synthesis

• requires iodine (dietary) to synthesize

• iodine enters follicular cell is combined with thyroglobulin in the lumen (iodination)

• protein undergoes conjugation and reenters the follicular cell by endocytosis

• proteolysis splits protein into T3 & T4

Thyroxine (T4)

• precursor to T3

Triiodothyronine (T3)

• active thyroid hormone

• reverse version is not active

Factors affecting thyroid concentration

• increased with young age, cold weather, physical activity, feeding

• decreased with disease/inflammation, NSAIDs/glucocorticoids/some plants

• excessive iodine can increase or decrease THs