Lecture 5 Slides Flashcards
Hormones released by anterior pituitary
TSH- thyroid ACTH- adrenal cortex FSH and LH- testes or ovaries GH- entire body (growth hormone) PRL (prolactin) - mammary glands Endorphins- pain receptors in the brain
In hypothalamus, neuro secretory cell releases hormones into what to get to anterior pituitary!
Blood vessel
Cell types in anterior pituitary
Corticotroph Thyrotroph Gonadotroph (FSH and LH) Lactotroph (mammotroph) Somatotroph
Hormone and staining characteristic:
Corticotroph
Corricotropin (ACTH)
Basophil
Hormone and staining characteristic:
Thyrotroph
Thyrotropin (TSH)
Basophil
Hormone and staining characteristic:
FSH gonadotroph
Follitropin (FSH)
Basophil
Hormone and staining characteristic:
LH-gonadotroph
Lutropin. (LH)
Basophil
Hormone and staining characteristic:
Lactotroph
Prolactin
Acidophil
Hormone and staining characteristic:
Somatotroph
Growth hormone
Acidophil
Three types of human anterior pituitary hormones
Corticotropin-related peptide hormones
Glycoprotein hormones
Somatomammotropin hormones
Corticotropin-related peptide hormones
Single small peptides derived from common precursor
Glycoprotein hormones
Composed of two dissimilar peptides. The alpha chain is similar in structure or identical. The beta chain differs with each hormone and confers specificity.
Somatomammotropin hormones
Single peptide chains with two or three SS (disulfide) bonds; no carbohydrate
Four Corticotropin-related hormones of anterior pituitary
Alpha-melanocyte stimulating hormone (alpha-MSH or alpha-melanotropin)
Corticotropin (ACTH)
Beta-lipotropin (beta-LPH)
Beta-endorphin (beta-LPH) 61-91
Glycoprotein hormones in anterior pituitary
Follicle stimulating hormone
Luteinizing hormone
Thyrotropin
Somatomammotropin hormones
Prolactin
Growth hormone
Signaling systems of single chain proteins from anterior pituitary
ACTH - cAMP
GH- STAT
PRL - STAT
Signaling systems of anterior pituitary glycoproteins
LH, FSH, and TSH - all cAMP
STAT
Signal transduces and activator of transcription
CAMP
Cyclic adenosine 5’-monophosphate
Four parts of pituitary gland
Pars distalis (anterior) Pars intermedia Pars nervosa
Hormones released by pars nervosa (posterior)
ADH
Oxytocin
Hormones released by pars intermedia
Basophils: ACTH and MSH
Hormones released by pars distalis
Acidophils: prolactin and GH
Basophils : TSH, ACTH, FSH, LH/ICSH
How do hormones travel from hypothalamus to anterior pituitary?
Portal system
How do hormones travel from hypothalamus to posterior pituitary
Hypothalamohypophyseal tract
What is pars tuberalis
Between pituitary gland and hypothalamus
Which neuron communicates between hypothalamus and anterior pituitary
Parvocellular neuron
Steps from parvocellular neuron to systemic circulation
Parvocellular neuron Axonal transport Median eminence (CRH, TRH, LHRH, GHRH, SS, DA) Long portal veins Anterior pituitary ACTH, TSH, LH/FSH, GH, PRL Systemic circulation
Hormones sent by hypothalamus to anterior pituitary
CRH, TRH, LHRH, GHRH, SS, DA
Hormones released by anterior pituitary
ACTH, TSH, LH/FSH, GH, PRL
Which neuron communicates between hypothalamus and posterior pituitary
Magnocellular neuron
Steps from mango cellular neuron to systemic circulation
Magnocellular neuron
Axonal transport
Posterior pituitary
Systemic circulation
Hormones released by posterior pituitary
OT, AVP, NP
What are hypothalamic-hypophyseotropic nuclei
They represent a collection of various neurons with neuro endocrine function that lie in the lateral wall of the third ventricle
What sends axons to median eminence
Small-sized neurons. Hormones are stored in small vesicles in the terminals next to capillary plexus.
How do hormones leave median eminence
Hormones are released into the capillary network and carried to the anterior pituitary.
What are releasing factors? What do they regulate?
Individual hypothalamic hormones
Regulate specific anterior pituitary cell types
Anatomical evidence in support of portal-vessel chemo transmitter hypothesis
- blood flows to the anterior pituitary from the primary capillary plexus located in the median eminence
- in contrast to the posterior pituitary, there is little secretomotor innervation of the anterior pituitary
Experimental evidence in support of portal-vessel chemo transmitter hypothesis
- lesions in the hypothalamus and median eminence produce atrophy of specific endocrine glands
- electrical stimulation of localized regions in the anterior hypothalamus evokes secretion of specific anterior pituitary hormones.
- transfection of the pituitary stalk, with the insertion of an impermeable barrier to prevent regeneration of the portal vessels, results in failure of gonadal, thyroid and adrenal function, and stunts growth
- transplantation of anterior pituitary into a well-vascularized region remote from its original site fails to restore target organ function in hypophysectomized animals; however, replacement under the median eminence, so that the anterior pituitary becomes recascularized by the portal vessels, reverses the decline.
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
Start with TRH, thyrotropin releasing hormone
TRH-paraventricular nuclei-TSH and prolactin-thyrotroph
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
LHRH, Luteinizing hormone-releasing hormone
LHRH-anterior and medial hypothalamus; preoptic septal areas-LH/FSH-gonadotroph
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
Corticotropin-releasing hormone
CRH-medial parvocellular portion of paraventricular nucleus-adrenocorticotropic hormone- corticotroph
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
Growth hormone releasing hormone
GHRH-arcuate nucleus, close to median eminence- GH- somatotroph
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
Somatostatin or growth hormone inhibiting hormone
Somatostatin- anterior paraventricular area-GH-somatotroph
Hypophysiotropic hormone-predominant hypothalamic nuclei-anterior pituitary hormone controlled-target cell
Dopamine
Dopamine- arcuate nucleus- prolactin- lactotroph
cDNA sequence of TRH precursor encodes how big a protein
Of 255 aa
What sequence occurs five times in the cDNA sequence of the TRH precursor
Gln-His-Pro-Gly
In cDNA sequence, each tetra peptide is flanked by
paired basic residues (Lys Arg or Arg Arg)
TRH precursor generates how much TRH
Five TRH molecules from each precursor protein
Hormones released by hypothalamus (6)
GnRH, GHRH, SS, TRH, DA, CRH
GnRH is precursor to what from AP
FSH and LH (upregulates)
GHRH is precursor to what AP hormone
GH (upregulates)
SS is precursor to what AP hormone
GH (downregulates)
TRH is precursor to what AP hormone
TSH (upregulates)
DA is precursor to what AP hormone
Prolactin (downregulates)
CRH is precursor to what AP hormone
ACTH(upregulates)
Function of FSH and LH
Go to gonads
Germ cell development
Secrete hormones: female, estrogen and progesterone/male, testosterone
Function of GH
In liver and other cells : secrete IGF-I
Many organs and tissues: protein synthesis, carb and lipid metabolism
TSH function
Thyroid: secretes thyroxine and triidothyronine
Prolactin function
Breasts: breast development and milk production(in male may facilitate reproductive function)
ACTH function
Adrenal cortex: secretes cortisol
Physiological roles of ACTH (5)
- Corticotropin stimulates adrenal cortex to secrete cortisol, adrenal androgens and in part mineralcorticoids
- Corticotropin is a 39 amino acid peptide synthesized as a part of 241 AA precursor molecule pro-opiomelanocortin (POMC)
- processing of precursor is species and tissue specific
- the first 18 AA of corticotrophin has full biological activity
- ACTH receptor is a GPCR with cAMP secondary messenger
What controls ACTH secretion? When is it lowest and highest?
It is under circadian control.
Lowest at midnight, peaks in the morning and declines in afternoon
What stimulates ACTH release?
Hypothalamic CRH and vasopressin
What physiological issues stimulate ACTH release?
Stress, pain, fear, fever, and hypoglycemia
What do glucocorticoids released from adrenals influence by feedback control.
Pituitary corticotrophs, hypothalamic neurons, glucocorticoids swnsirice neurons of hippocampus
What kind of pattern does ACTH secretion have
Pulsatile
What causes Cushing syndrome
Excess of adrenal cortical function, often caused by pituitary corticotroph adenoma
What does excess of ACTH release cause
Increases adrenal hormone secretion (cortisol) without proper feedback effects
Clinical features of excess ACTH release
Weight gain
Moon face
Centripetal obesity
Peripheral (arms/legs) myopathy, diabetes, etc.
Ehat does diagnosis of excess ACTH release involve
Measurements of the levels of ACTH and cortisol in circulation
What is TSH composed of
Two subunits (alpha and beta) with beta subunit providing specificity of the hormone
What is a hormone? What is required for its biological activity?
A glycoprotein
Sugar moieties are required
How is thyrotropin (TDH) released? When is it at highest and lowest levels?
Released in circadian fashion
Levels are highest at 8 PM, remain high at night and decline in the morning
How are TDH levels measures
By radioimmunoassay (RIA)
What receptor does TDH activate
7TM G-protein linked receptor
Major early stimulator effects of TSH on thyroid follicular cells
Adenylate Cyclase
Endocytosis of colloid
Mitochondrial respiration and cell metabolism
Major late stimulators effects of TSH on thyroid follicular cells
Iodide uptake
Protein synthesis
DNA replication and mitotic activity
Two inactivating mutations in TSH receptor
Del AC 655
G–>C + 3IVS6
What do receptors for TSH, FSH and LH have in common
An exceptionally large N-terminal domain
Four disorders of the thyrotropin
- TSH deficiency due to mutation in the gene encoding the beta subunit
- human thyroid-stimulating immunoglobulin binding to TSH receptor of thyroid gland
- Hashimoto’s thyroiditis
- mutation in gene encoding TSH receptor