Lecture 20: Endocrinology Flashcards
What is an endocrine axis?
A chain of hormones regulating a system, typically contained in the hypothalamus, pituitary, and target organ.
Primary endocrine disease
Originates in the target organ of an endocrine axis
Secondary endocrine disease
Originates the the hypothalamus or pituitary, or is caused off-axis.
General pharmacological endocrine axis features.
- Hypothalamic hormones
- Trophic hormones from pituitary
- Action at target organ(s)
Protein vs steroid hormones
Proteins: actively stored and secreted into fenestrated capillaries, target surface receptors
Steroids: require carrier proteins in the blood, synthesized from cholesterol. Target surface, intracell., or nuclear receptors
How does adipose tissue act as a hormone source?
Adipose tissue itself produces many hormones, primarily leptin and adiponectin which are satiating/anorexigenic, inflammatory/anti-inflammatory.
Parts of the pituitary gland
- Neurohypophysis (posterior)
- Adenohypophysis (anterior)
Neurohypophysis
Neuroectoderm origin. Made of descending axons from supraoptic/paraventricular hypothalamic nuclei. Releases ADH, oxytocin.
Pituicytes
Resident glia of the neurohypophysis. Control hormone release to surrounding capillaries.
Structures of the neurohypophysis
- Median eminence
- Infundibular stalk
- Pars nervosa
- Herring bodies (axonal endings dilated with NTs)
Adenohypophysis
Originates from oral ectoderm. Responds to hypothalamic hormones released to the hypophyseal portal system.
Cells of the adenohypophysis
Pars distalis
1. Acidophils -> somatotropin, prolactin
2. Basophils -> ACTH, TSH, FSH, LH, β-endorphin
3. Chromophobes
Pars intermedia cells -> melanocyte-stimulating hormone
Structures of the adenohypophysis
- Pars tuberalis
- Pars intermedia
- Pars distalis
Where is the pituitary located?
The pituitary is at the base of the brain, encapsulated by sphenoid bone in the sella turcica cavity with an apical stalk to the hypothalamus.
Thyroid gland
Composed of many thyroid follicles, which are epithelial-enclosed accumulations of colloid. Uptakes iodine from blood, sequesters with thyroglobulin (colloid, Tyr-containing). Mono-iodin. Tyr + di-iodin. Tyr (MIT/DIT) sum for T3, T4.
Cells of the thyroid gland
Majority: follicular cells containing thyroglobulin -> T3, T4
Minority: parafollicular cells aka C-cells -> calcitonin
Parathyroid gland
Primarily made of chief cells -> PTH, also contains oxyphil cells
Pineal gland
Gland in brain with pinealocytes producing melatonin. Regulates circadian sleep/wakefulness. Accumulates concretions of corpora arenacea (brain sand)
Endocrine pancreas
Islets of Langerhans. In order of decreasing frequency, cells include:
β cells -> insulin
α cells -> glucagon
γ cells aka PP cells -> pancreatic polypeptide
δ cells -> somatostatin
Other cells -> ghrelin (hunger)
Adrenal glands
Consists of 2 embryological parts: cortex + medulla (mesenchyme + NCCs aka ectoderm). Produces corticosteroids, epi, and NE
Adrenal cortex layers
Outer to inner:
1. Zona glomerulosa -> mineralocorticoids (aldosterone)
2. Zona fasciculata -> glucocorticoids (cortisol)
3. Zona reticularis -> androgens
Adrenal medulla
Derived from neural crest cells. Contains 2 types of chromaffin cells producing epi and NE. Has dual blood supply from cortical capillaries and long cortical aka medullary arteries (arterioles).
DNES
Diffuse Neuroendocrine System. Refers to scattered cells in other organs that release endocrine hormones, especially in the GI system.
APUD cells
Amine Precursor Uptake + Decarboxylation cells. Part of DNES, produce polypeptide hormones from amine precursors via decarboxylases.
Sex hormones
Includes estrogen, progesterone, testosterone. Can be free or carrier bound; primarily produced by Leydig cells in testis or ovarian follicle granulosa cells/corpus luteum.
Sex hormone carriers
- Sex Hormone Binding Globulin (SHBG)
- Albumin
- Corticosteroid Binding Globulin (CBG) aka transcortin
Estrogens
4 significant types:
1. E1 (estrone)
2. E2 (estradiol)
3. E3 (estriol)
4. E4 (estetrol)
Sex hormone receptors
- Estrogen Receptors (ERs, α/β = nuclear receptors)
- Androgen receptors (for t-sterone)
- Nuclear progesterone receptors (for progesterone, types A/B/C)
How is sex hormone production controlled?
Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates FSH/LH secretion by ant. pituitary basophils. Inhibin-B inhibits FSH/LH release (negative feedback).
Menstrual cycle
Cyclical hormone variation due to temporary loss of inhibin-B negative feedback.
Major endocrine axes
- HPA (adrenal)
- HPT (thyroid)
- HPG (gonads)
- HPS (somatic)
- HPP (prolactin)
Characteristics of endocrine cells
Endocrine cells secrete hormones basally, i.e. into the blood, in order to act at a distance.
Common endocrine features
- Fenestrated capillaries (even in pituitary despite BBB)
- Disturbed polarity (lack of apical domain due to no lumen)
- Carrier proteins for blood transmission
Hormone types by gland origin
Protein hormones come from epithelial origin glands
Steroid hormones come from mesenchymal origin glands
Releasing/inhibiting factors
Positive/negative feedback in the endocrine system
HPA axis
H: Corticotropin releasing hormone
P: adrenocorticotropic hormone (ACTH), corticotrophs
A: cortisol, etc., adrenals
HPT axis
H: Thyroid Releasing Hormone (TRH)
P: Thyroid Stimulating Hormone (TSH), thyrotrophs
T: T3/T4 from thyroid.
HPG axis
H: GnRH
P: LH/FSH, gonadotrophs
G: estrogen/estradiol/progesterone from ovaries, testosterone from testes; inhibin from both.
HPS axis
H: GnRH
P: Growth Hormone from somatotrophs
S: Various target organs e.g. liver; somatostatin inhibits GnRH
HPP axis
H: Dopamine
P: Prolactin from lactotrophs
P: Lactation by mammary glands
Hypothalamus
Major parts: supraoptic + paraventricular nuclei (SON, PVN)
2 projections to the pituitary:
1. Magnocellular (axons to neurohypophysis)
2. Parvocellular (releasing hormone secretion to adenohypophysis via pituitary portal circulation)
Goiter
Enlarged thyroid due to iodine deficiency
Graves’ disease
Autoimmunity to TSH receptors.
Endocrine organ aging
Fibrosis normally occurs with age from collagens and other ECM molecules.
Testis
FSH -> Sertoli cells -> inhibin-B, Androgen Binding Protein (ABG), Anti-Müllerian Hormone
LH -> Leydig cells -> t-sterone
Sex endocrine organ development
Ovary/testis develop from bipotential mesonephric mesenchyme. Testis req. testis-determining factor (TDF) from SRY.
Mesonephric (Wolffian) duct -> epididymis, vas deferens
Paramesonephric (Müllerian) duct -> oviduct, uterus
DHT drives external male pattern genitalia.
Endocrine organs embryonic origins
Surface ectoderm -> ant. pituit.
Neural ectoderm -> hypothal., post. pituit., pineal
Endoderm -> pancreas, thyroid, parathyroid
Mesoderm -> ovary/testis, adrenal cortex
Ectomesenchyme (NCCs) -> adrenal medulla
