chemical compounds synthesized and released in small amounts into systemic circulation to mediate a physiological function
4
What forms do hormones take?
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• steroids
• proteins
• amines
5
What is the chemical structure of steroids?
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Derivatives of cholesterol (hormones from gonads and adrenal)
• Lipid soluble
• Can cross the phospholipid bilayer
• activate receptors inside cells or turn genes on/off
6
What are the main types of non-steroid hormones?
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amines and proteins
7
Structure of protein nature non-steroid hormones
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• Synthesized in rough ER as prohormones
• packaged in vesicles till release
• Most hormones have protein nature
• Hydrophilic
• Bind to cell surface receptors and activate secondary messengers to induce physiological function
8
Structure of amines
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derived from tyrosine
• thyroid hormones and adrenaline/noradrenaline
9
What is the predominant mechanism for hormone release regulation?
What is the function of acidophils in the adenohypophysis?
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Acidophils secrete growth hormone (GH) and prolactin (PRL).
30
Which hormone is produced by somatotrophs in the adenohypophysis?
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Somatotrophs secrete growth hormone (GH).
31
Lactotrophs, aka lactotropes, produce what hormone
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prolactin (PRL)
32
What hormone does a gonadotroph produce?
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Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
33
Which hormone is produced by corticotrophs?
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Adrenocorticotropic hormone (ACTH)
34
What hormone does a thyrotroph produce?
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Thyroid-stimulating hormone (TSH)
35
What are chromophobes?
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Cells with lighter staining that contain some secretory granules.
36
Which cells are chromophobes?
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1. melanotrophs → melanocyte stimulating hormone (MSH)
2. stem cells → hormone producing cells + older chromophil cells that lost their secretory function
3. folliculo-stellate cells: have phagocytic and paracrine function
What hormones are carried by the unmyelinated axons in the neurohypophysis?
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Oxytocin and anti-diuretic hormone
from hypothalamus to nerve terminals to axonal distension (herring bodies)
39
What are herring bodies
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axonal distensions that store and release the hormones
40
What are pituicytes
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glial cells that provide supportive function to the axons
41
how do hormones go from the hypothalamus to the pituitary
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Anterior Pituitary - Portal System
→ Hypothalamic releasing/inhibiting hormones are released into a capillary plexus
→ travel down through portal veins
→ stimulate anterior pituitary hormone release
Posterior Pituitary - Nerve Tract
→ hormones sent down axon terminals in the pituitary stalk
→ directly to the posterior lobe for storage (Herring) and release
42
What is the hypothalamic–hypophysial portal system?
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transmission of hypothalamic peptides directly to anterior pituitary without systemic dilution
43
Which artery supplies blood to the posterior pituitary gland?
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The inferior hypophyseal artery.
44
What is the hypothalamus-pituitary-peripheral gland axis?
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• hierarchical system for endocrine function regulation
• organization allows central control over endocrine function
45
Functions of hypothalamus-pituitary-peripheral gland axis?
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untitled answer
46
How does the Hypothalamus control the anterior pituitary?
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through releasing/inhibitory hormones via hypothalamic-hypophysial portal system
What do sufficient sex steroid hormones do to FSH?
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Inhibits its release
63
What do sufficient sex steroid hormones do to LH?
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LH release is stimulated by high estrogen levels
during ovulation
positive feedback mechanism
64
What is the function of gonadotropins?
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promote testosterone secretion in males
promotes estrogen and progesterone secretion in females
65
Which hormone stimulates ovulation in females?
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FSH =growth of the ovarian follicles + regulate the ovulatory cycle
LH = ovulation, progesterone from corpus luteum, steroid release from ovaries
66
What do FSH and LH do in males?
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FSH = spermatogenesis
LH = testosterone release
67
What hormone aids in spermatogenesis in males?
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Follicle-stimulating hormone
68
What is the role of CRH in the synthesis of ACTH?
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CRH stimulates the adrenal cortex to produce ACTH.
69
How is ACTH synthesized?
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In response to corticotropin-releasing hormone (CRH)
• synthesized by corticotropes (POMC cells)
• from the prohormone precursor: proopiomelanocortin (POMC)
70
What is the diurnal rhythm of CRH and ACTH release?
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released in pulses following the diurnal rhythm
highest levels in the early morning
71
What are the functions of ACTH?
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1. binds to adrenal receptors + stimulates glucocorticoids. mineralocorticoids
• Aldosterone = regulating salt and water metabolism
• Glucocorticoids = metabolism and stress response
2. Growth/survival of cells in adrenal cortex
3. glucose metabolism and immune function
72
What are glucocorticoids?
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hormones produced by adrenal cortex
regulate metabolism and response to stress
73
What is the role of ACTH in the HPA axis?
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ACTH stimulates the release of cortisol from the adrenal cortex.
74
What is the negative feedback mechanism of CRH and ACTH?
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Cortisol inhibits CRH and ACTH secretion
Negative feedback mechanism
75
Which part of the brain controls the setpoint of the HPA axis?
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The hypothalamus
76
What is GH (somatotropin) synthesized by?
Show answer
Somatotrophs, released by hypothalamus
77
What is the primary hormone responsible for stimulating growth in humans?
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Growth Hormone
78
Regulation of GH via hormones?
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Balance between GHRH and Somatostatin
stimulatory: growth hormone-releasing hormone (more dominant)
inhibitory: somatostatin
79
What is the endocrine axis?
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hypothalamic-pituitary-liver axis
80
When is GH released?
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at sleep and during exercise
in pulsatile manner
81
What stimulates the production of IGF-1 in the liver?
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GH
82
What stimulates the secretion of growth hormone?
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Sleep, stress, hormones related to puberty, starvation, exercise, and hypoglycemia
83
What inhibits the secretion of growth hormone?
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• Somatostatin, somatomedins (IGF-1), obesity, hyperglycemia, and aging
• inhibits its secretion by stimulating somatostatin from the hypothalamus
84
Inhibition of GHRH
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inhibits its own secretion from the hypothalamus
85
What is the direct effect of growth hormone on adipose tissue?
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Lipolysis - for energy
fuels higher metabolism for other cells
86
What is the direct effect of growth hormone on the liver?
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Promotes gluconeogenesis and glycogenolysis
87
Effect of growth hormone on tissues?
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GH induced insulin resistance
• resistance increased in tissues
• less effective in moving glucose into cells
88
What is the indirect effect of insulin-like growth factor 1 (IGF-1)?
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• Promotes cellular metabolism
• Prevents cell death
• ↑ Rate of cell division / differentiation
• Promotes protein, RNA and DNA synthesis
• Increases linear growth via action on chondrocytes and osteoblasts
89
What is prolactin?
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hormone synthesized by lactotrophs in response to thyrotropin-releasing hormone (TRH)
90
What are the factors that increase prolactin secretion?
• mammary gland development + milk production.
• Inhibit ovulation + spermatogenesis via ↓ GnRH
• development of breast and mammary glands
• modulates reproductive and parental behavior
92
How does prolactin inhibit ovulation and spermatogenesis?
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By decreasing synthesis/release of GnRH
93
What is the effect of prolactin deficiency on milk production in the breast?
1. Congenital
2. Secondary to:
• head trauma/thrombus
• radiation, autoimmune disorders/infections
• pituitary tumors that compress the pituitary gland
112
ACTH in adult hypopituitarism?
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deficiency leading to adrenal insufficiency
113
TSH in adult hypopituitarism?
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Decreased thyroid hormone production
114
Gonadotropin in adult hypopituitarism?
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deficiency leading to hypogonadism and declining sexual functions
115
GH in adult hypopituitarism?
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Decreased GH = decrease fat mobilization, weaker muscles and lower bone density
116
ADH in adult hypopituitarism?
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ADH deficiency leading to diabetes insipidus
117
Melanocortin in adult hypopituitarism?
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Melanocortin deficiency leading to abnormal pallor
118
Causes of dwarfism relating to hormones
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1. Panhypopituitarism during childhood - 70%
2. Deficiency of GH - 30 %
3. Deficiency of somatomedin C
119
Effects of Panhypopituitarism during childhood
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• Decreased rate of body development
• appropriate proportions to each other.
• lack adult sexual functions due to gonadotropins deficiency
120
What is the primary cause of dwarfism due to deficiency of growth hormone?
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slower growth rate but attain sexual maturity and can reproduce
121
What is the effect of somatomedin C deficiency on individuals?
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short stature and slower growth
122
What are the dental complications of hypopituitarism?
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– Maxilla and mandible are smaller than the normal
– delayed exfoliation of primary teeth
– delayed eruption of permanent teeth
– shorter roots and crowding of permanent teeth
123
Management of GH deficiency?
Show answer
Synthetic human somatotropin
124
Indications for using synthetic human somatotropin?
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GH deficiency in children with growth retardation + adults with confirmed deficiency
125
Adverse effects of synthetic human somatotropin?
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Increased risk of diabetes, edema, and pain at injection site
126
What is hyperpituitarism?
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Hypersecretion of pituitary hormones
127
Causes of Hyperpituitarism
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1. Pituitary adenoma (common)
2. Congenital
• genetic mutation in single cell yielding hormone-secreting tumor
128
Clinical presentations of hyperpituitarism?
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Adulthood: Acromegaly.
Childhood: Gigantism
129
What are the clinical presentations of hyperpituitarism in childhood?
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Gigantism
130
What is the primary cause of acromegaly?
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GH-secreting pituitary adenoma
multiple due to high levels of IGF-1
131
What are the clinical manifestations of acromegaly?
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1. Organomegaly: heart, tongue, kidney and vocal cords
2. Joint pain and hunched back
3. onset of insulin resistance
132
Orofacial presentation of acromegaly
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• Thick lips
• mandibular overgrowth
• prognathism
• jaw thickening
• maxillary widening,
• drifting of teeth/malocclusion.
• enlargement of forehead bones and nose
133
What is prognathism?
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The protrusion of the lower jaw forward
134
Which bones are thickened in acromegaly?
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Frontal bones
135
What is the primary characteristic of gigantism?
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Rapid growth of all body tissues that can occur before adolescence
Hyperglycemia that can lead to destruction of beta cells and diabetes
138
Management of GH over-production?
Show answer
A) Surgical
B) Pharmacological: Somatostatin = growth hormone-inhibiting hormone
139
Indication of Somatostatin as growth hormone-inhibiting hormone
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treatment of acromegaly
140
What are the adverse effects of pharmacological management of GH over-production?
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GI symptoms (abdominal pain, diarrhea, nausea and vomiting)
141
What is the etiology of central diabetes insipidus?
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Damage to the hypothalamus/pituitary gland, congenital defect leading to decreased ADH level.
142
What gland is responsible for producing ADH in central diabetes insipidus?
Show answer
Pituitary gland
143
What are synthetic analogues of ADH?
Show answer
Vasopressin & Desmopressin
144
What is the indication for the use of Vasopressin and Desmopressin?
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Management of central diabetes insipidus
145
What is the adverse effect of Desmopressin?
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Desmopressin may cause xerostomia
146
What is the toxicity associated with Desmopressin?
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Toxicity is associated with hyponatremia
147
Causes of Syndrome of Inappropriate Anti-diuretic Hormone Secretion (SIADH)?
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Increased ADH release
• CNS disorders, head trauma, injury
• ectopic production of ADH in lung malignancies
• drugs: carbamazepine and cyclophosphamide
148
Pathophysiology of SIADH?
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excessive free water retention + continued urinary Na+ excretion
= hyponatremia and expansion of plasma volume
149
Treatment of SIADH?
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Fluid restriction (first line), salt tablets and ADH antagonists