Jan 8 - Hypothalamus & Pituitary Hormones Flashcards
What is superior to the pituitary gland?
The hypothalamus
Describe the anatomy of the pituitary gland from the hypothalamus
The pituitary gland descends from the hypothalamus via the hypophysial stalk, which turns into the posterior pituitary. The pars intermedia separates the anterior and the posterior pituitary
Name two posterior pituitary hormones
Vasopressin
Oxytocin
What is vasopressin?
Aka antidiuretic hormone (ADH)
It conserves body water and regulates osmotic pressure of body fluids. Dehydration leads to increase in osmolarity, activates osmoreceptor in brain and ADH secretion. ADH acts on kidney cells (distal convoluted tubule and medullary collecting ducts) via cell surface receptors and cAMP formation; enhances water permeability and reabsorption
What is the result in a deficiency of ADH?
Central diabetes insipidus (vs. nephrogenic DI) - inability to retain water, excess thirst, frequent urination
What are the treatments for central diabetes insipidus?
Drugs (clofibrate) to increase ADH secretion and (chlorpropamide) to increase kidney response to ADH; diuretics and dietary salt restriction to increase urine output
What is the result in an excess of ADH?
Excess water retention, headache, drowsiness, nausea
What are the treatments available for an excess of ADH?
Drugs (butorphanol) to decrease ADH secretion and (demechlocycline) to reduce kidney response to ADH
What is oxytocin?
It stimulates the contraction of smooth muscle cells, particularly that of the mammary gland and uterus (important for female reproduction). Upon nursing, suckling reflex stimulates oxytocin release, which causes contraction of myoepithelial cells in breast to expel milk. During childbirth, oxytocin release during labour to stimulate rhythmic uterine contractions; clinically used to induce labour and therapeutically postpartum to decrease bleeding
What are major hypothalamic (hypophysiotropic) hormones? What are their effects on the anterior pituitary?
Corticotropin-releasing hormone (CRH) increases ACTH.
Thyrotropin-releasing hormone (TRH) increases TSH and prolactin
Gonadotropin-releasing hormone (GnRH) increases LH and FSH
Growth hormone-releasing hormone (GHRH) increases GH
Somatostatin decreases GH
Dopamine decreases prolactin
What is TRH?
3 amino acid-hormone (E-H-P)
What is LHRH?
A 14 amino acid-hormone
What is dopamine?
One amino acid; hydroxylated and decarboxylated tyrosine
Explain the feedback regulation of anterior pituitary hormones
The hypothalamus releases a releasing or inhibitory factor that acts on the pituitary. Releasing factors cause the pituitary to release hormones that promote the release of tropic hormones from endocrine glands, and inhibit the further release of releasing factors from the hypothalamus. Tropic hormones, aside from acting on target tissues, either further activate the release of pituitary hormones or inhibit it, as well as releasing factors from the hypothalamus
Name 5 anterior pituitary hormones. What do they act on?
Prolactin acts on the breast to produce milk. Growth hormone acts on the liver to activate the secretion of IGF-1, which acts on the bones and soft tissue to produce growth. TSH acts on the thyroid gland to activate the secretion of T4 and T3. ACTH acts on the adrenal cortex to activate the secretion of cortisol. Gonadotropins (LH/FSH) act on the gonads to produce sex hormones and gamete production
What is the source of growth hormone?
Somatotropes and somatomammotropes of the anterior pituitary
What are the actions of growth hormone?
Decreases insulin sensitivity, increases lipolysis, increases IGF-1 secretion. GH and IGF-1 both increase protein synthesis and epiphyseal (bone) growth
What controls growth hormone?
Stimulated by GHRH, hypoglycemia, exercise, certain amino acids, sleep. Inhibited by somatostatin, IGF-1 (negative feedback), hyperglycemia
What is the result of an excess of growth hormone?
Somatotrope tumor. If GH excess occurs early in life, results in gigantism (rare). If GH excess occurs after body growth stopped, results in acromegaly (excess soft tissue hyperplasia)
What are the treatments available for excess of growth hormone?
Tumor removal, SS analogues, GH receptor antagonist
What are the causes of a deficiency of growth hormone?
Hypothalamic (GHRH deficiency) and pituitary lesions (tumours, injury, infection, congenital and genetic defects) leading to primary GH deficiency.
What are other causes of retarded growth (when GH is good)? What are the treatments available?
Other causes of retarded growth include Laron Dwarfs (GH receptor defect in target tissues) and African pygmies (IGF-1 deficiency). Hypochondroplasia (achondroplasia), non-proportional short stature. GH and IGF-1 replacement therapy is an option for the first two
What is the result of primary GH deficiency?
Proportinal short-stature (if it occurs early in life)
Adult hypopituitarism: weakness, fine wrinkling and pale skin, loss of sex drive, genital atrophy, menstrual cycle cessation
What is the source of prolactin?
Lactotropes and somatomammotropes of anterior pituitary
What are the actions of prolactin?
Promotes growth and function of mammary gland-milk production (also participates in suckling reflex). Increased maternal behaviour. Inhibits gonadotropin secretion/action in gonads - steroidogenesis. Numerous effects in lower species but not well studied in humans
What controls prolactin?
Predominately inhibited by hypothalamic dopamine. Also stimulated by oxytocin, TRH, VIP and estrogen
Explain the hormone changes in suckling reflex
Infant suckling activates mechanoreceptors in the nipples. Activation is received in the hypothalamus, which acts on the posterior pituitary and decreases dopamine secretion. The posterior pituitary increases the oxytocin secretion, which increases contraction of myoepithelial cells, which increases milk ejection. The decrease in dopamine secretion causes the anterior pituitary to secrete more prolactin which increases milk production
What are the causes of an excess of prolactin?
Hyperprolactinemia: most common form of pituitary hyperfuction caused by adenomas of lactotropes (most common form of pituitary tumour). Dopamine receptor blockers (some psychiatric medications). Stress, high physical activities, under weight
What are the consequences of an excess of prolactin in females?
Anti-gonadal action causes secondary amenorrhea (cessation of menstrual cycle), hence, infertility. Galactorrhea (inappropriate milk production)
What are the consequences of an excess of prolactin in males?
Impotence, decrease sperm count, infertility
What treatments are available for an excess of prolactin?
Dopamine agonists (cabergoline and bromocryptine/parlodel) suppress prolactin secretion and shrink prolactinomas
What is the source of gonadotropins - luteinizing hormone (LH) and follicle stimulating hormones (FSH)
Gonadotropes
What are the actions of LH and FSH
Reproductive hormones acting on the gonads. LH stimulates sex steroidogenesis: estrogen, progesterone and testosterone. FSH stimulates growth of ovarian follicles and sperms
What controls LH and FSH?
Stimulated by hypothalamic GnRH, and high levels of estrogen. Inhibited by inhibin (from gonads), low levels of estrogen, progesterone and testosterone
What is the result of an excess of gonadotropins? How is it treated?
Hypersecretion of GnRH and gondatropins - true precocious puberty. Treatment with supra-agonist of GnRH. Gonadotrope tumours are rare
What is the result of a deficiency of gonadotropins? How is it treated?
GnRH deficiency (Kallmann’s syndrome). Hypopituitarism. Reproductive failure due to insufficiency of sex steroids, abnormal development of genitalia and accessory sex organs, abnormal menstrual cycle, amenorrhea, infertility, delayed puberty. It is treated with GnRH and steroid replacement therapy
What is the source of thyroid stimulating hormone (TSH)?
Thyrotropes
What is the action of TSH?
Stimulates iodine uptake and production of thyroid hormones (T4 and T3) of thyroid gland. T3 and T4 for every production and maintains metabolic rate (heat), body growth and organ differentiation
What controls TSH?
It is stimulated by hypothalamic TRH. Negative feedback of T3 and T4 inhibit it
What is the result of excess of TSH?
TSH-secreting pituitary tumour causes hyperthyroidism but not the common cause of hyperthyroidism
What are the common causes of hyperthyroidism?
Subacute thyroiditis. Toxic adenoma (nodular). Graves disease. Autoimmune antibodies.
What is Graves disease?
An autoimmune disorder characterized by thyroid stimulating immunoglobins (TSI) which stimulate T3/T4 production
What are the symptoms of hyperthyroidism?
Weight loss, heat intolerance, high BMR, heart failure, myopathy (muscle weakness due to excess protein breakdown)
How is hyperthyroidism diagnosed?
High T3/T4 and low TSH
How is hyperthyroidism treated?
Inhibitors of T3/T4 production, e.g., thiocarbamides, radioiodine (131), anti-inflammatory agents
What is the result of TSH deficiency?
Hypothyroidism: congential abnormality of hypothalamus-pituitary axis (TRH/TSH) deficiency); autoimmune thyroiditis (Hashimoto’s disease); iodine (dietary) deficiency
What is the result of a dietary deficiency of iodine?
Insufficient T3/T4 and decrease negative feedback leads to elevated TSH causing thyroid hypertrophy (goiter)
What are the symptoms of hypothyroidism?
Myxedema in adults: low BMR, sparse hair, dry & yellow skin, cold intolerance, husky & low voice, poor memory, mental instability (myxedema madness), abnormality in mentrual function. Cretinism in children: dwarf, potbellied and mental retardation
How is hypothyroidism treated?
T3/T4 replacement therapy, dietary iodine
What is the source of adrenocorticotropic hormone (ACTH)
Corticotrope. Cleavage product (by prohormone convertases PC1 and PC2) of larger precursor - pro-opiomelanocortin (POMC) gives rise to ACTH, MSH, beta-endorphin, lipotropin
What are the actions of ACTH? MSH? Beta-endorphin?
ACTH: stimulates adrenal cortex to produce glucocorticoids, mineralcorticoids and sex steroids. MSH: stimulates melanin and melanocytes (skin color). Beta-endorphin: morphine-like analgesic neurotransmitter (pain
What controls ACTH?
Stimulated by hypothalamic CRF. Negative feedback only by glucocorticoids
What is DHEA?
The main source of androgens in femails
What is aldosterone?
It affects the kidneys to regulate water and salt metabolism
What is cortisol?
Increases metabolic fuels: blood glucose, amino acids and fatty acids
What causes an excess of ACTH?
Secondary adrenal hyperfunction - 70% (e.g., Cushing’s syndrome): ACTH-secreting microadenomas of pituitary, hypersecretion of hypothalamic CRF, ectopic production of ACTH by non-pituitary tumors
What are the consequences of excess of ACTH?
Elevated glucocorticoids
Elevated mineralcorticoids
Elevated androgens
What is the result of elevated glucocorticoids?
Excess protein catabolism, thin subcutaneous tissues, poor muscle development, loss of bone mass.
Characteristic body fat re-distribution in abdomen and upper back (buffalo hump).
Elevated gluconeogensis, resulting in hyperglycemia leading to type II diabetes
What is the result of elevated mineralcorticoids?
K+ depletion, excess Na+ and water retention, hypertension
What is the result of elevated androgens?
In boys, it causes precocious development of secondary sex characteristics without testicular growth (precocious pseudopuberty). In girls, pseudohermaphroditism, which can be treated by the suppression or removal of tumours
Describe ACTH deficiency
Secondary adrenal insufficiency caused by decreased CRF and/or ACTH at the hypothalamus-pituitary axis. Excess Na+ loss, hypotension, abnormal metabolism of protein, carbohydrate and fat; fatal shock following minor shock
What is the treatment available for ACTH deficiency?
Cortisol, aldosterone replacement
