ENDOCRINOL
, ENDOCRINOLOGY
NATURE OF HORMONES
• Major classes of hormones:
o Amino acid derivatives – dopamine, catecholamines; cell-surface
membrane receptor interaction
o Small neuropeptides – GnRH, TRH; cell-surface membrane receptor
interaction
o Large proteins – insulin, LH, PTH; intracellular nuclear receptor interaction
o Steroid hormones – cortisol, estrogen; intracellular nuclear receptor
interaction
o Vitamin derivatives; intracellular nuclear receptor interaction
• Hormones and receptor families:
o Glycoprotein hormone family
§ Heterodimers that have an alpha-subunit in common; the beta-
subunits are distinct and confer specific biological functions
• The 3D structure of beta subunits is similar, reflecting the
locations of conserved disulfide bonds that restrain protein
conformation
§ Receptors
• Examples of receptor cross-talks for GPCRs
o TSH binds with high specificity to TSH-R but also
minimally with LH- and FSH-R
o Very high levels of hCG during pregnancy stimulate
the TSH-R and increase TH levels resulting in a
compensatory decrease in TSH
o IGF-I and IGF-II have structural similarities but have
diQerent receptors; nonetheless, high [IGF-II
precursor] produced by certain tumors such as
sarcomas, can cause hypoglycemia because of
binding to insulin and IGF-I receptors
• Nuclear receptor families
o Division:
§ Type 1 (GR, MR, AR, ER, PR) – bind steroids
§ Type 2 (RAR, PPAR, TR, VDR) – bind TH, VitD,
retinoic acid or lipid derivatives
o Specificity:
§ Hormone binding is usually specific for only
one type of receptor
§ Exception: GC and MC receptors
• Hormone synthesis and processing
o 1. Transcription
o 2. mRNA
o 3. Proteins
o 4. Post-translational protein processing
, o 5. Intra-cellular sorting
o 6. Membrane integration or secretion
§ POMC into ACTH
§ Proglucagon into glucagon
§ Pro insulin into insulin
§ Pro-PTH into PH
o 7. Peptide hormones are then stored into secretory granules
§ Steroid hormones diQuse into the circulation as they are produced
o 8. As these granules mature, they are poised beneath the PM for imminent
release into the circulation
o 9. The stimulating hormone is usually a releasing factor that induces rapid
changes in Ca2+ intracellular levels leading to secretory granule fusion and
release of the peptides
o 10. Degradation rate dictates the rapidity with which an hormonal signal
decays: some hormonal signals are evanescent (SST), others are long-lived
(TSH)
§ Very important for replacement therapy
o 11. In the circulation, many hormones are found couples with serum
binding proteins
§ TH4 and 3 binding to TBG, albumin an TBPA
§ Cortisol binding to CBG
§ Androgen and estrogen binding to SHBG
o 12. These interactions provide an hormonal reservoir, preventing the
otherwise rapid degradation of unbound hormones; restrict the hormones
to certain sites; and modulat the free hormone concentration
• Hormone receptors
o Membrane receptors
§ Major groups:
• GPCRs – large proteins, minerals, small peptides, aa
• TKR – insulin and other GFs
• Cytokine receptors – GH and PRL
, • Serine kinase receptors – MIS, BMPs, Gfbeta
o Nuclear receptors
§ Classification based on nature of ligands:
§ Function: mainly increasing or decreasing gene transcription
§ Location:
• Cytoplasm – GC receptors
• Nucleus – TH receptors
• Hormonal function
o Growth
§ Pathological:
• Short stature: GH deficiency, hypothyroidism, Cushing’s
syndrome, precocious puberty, malnutrition
o Maintenance of homeostasis
§ Most important ones:
• TH – controls about 25 of basal metabolism in most tissues
• Cortisol – permissive action for many hormones in addition
to its many functions
• PTH – regulates Ca2+ and PO4 levels
• Vasopressin – regulates serum osmolarity by controlling
renal free-water clearance
• MC – control vascular volume and [serum electrolytes]
• Insulin – maintains euglycemia in the fed and fasted state
o Reproduction
§ Stages of reproduction:
• 1. Sex determination during fetal development
• 2. Sexual maturation during puberty
• 3. Conception, pregnancy, lactation and child rearing
• 4. Cessation of reproductive capability at menopause
§ Hormones involved:
• LH, FSH
• Estrogen, progesterone
• Prolactin, oxytocin
• Hormonal feedback regulatory systems
o Paracrine and autocrine control
§ Paracrine – factors released by one cell that
acts on the adjacent cell in the same tissue
§ Autocrine – action of a factor on the same cell
from which it is produced
o Hormonal rhythms
§ Menstrualcycle
§ Circadian cycle
§ GnRH pulse frequency – regulating LH and FSH
secretion
• Pathological mechanisms
o Hormone excess
§ Causes:
, ENDOCRINOLOGY
NATURE OF HORMONES
• Major classes of hormones:
o Amino acid derivatives – dopamine, catecholamines; cell-surface
membrane receptor interaction
o Small neuropeptides – GnRH, TRH; cell-surface membrane receptor
interaction
o Large proteins – insulin, LH, PTH; intracellular nuclear receptor interaction
o Steroid hormones – cortisol, estrogen; intracellular nuclear receptor
interaction
o Vitamin derivatives; intracellular nuclear receptor interaction
• Hormones and receptor families:
o Glycoprotein hormone family
§ Heterodimers that have an alpha-subunit in common; the beta-
subunits are distinct and confer specific biological functions
• The 3D structure of beta subunits is similar, reflecting the
locations of conserved disulfide bonds that restrain protein
conformation
§ Receptors
• Examples of receptor cross-talks for GPCRs
o TSH binds with high specificity to TSH-R but also
minimally with LH- and FSH-R
o Very high levels of hCG during pregnancy stimulate
the TSH-R and increase TH levels resulting in a
compensatory decrease in TSH
o IGF-I and IGF-II have structural similarities but have
diQerent receptors; nonetheless, high [IGF-II
precursor] produced by certain tumors such as
sarcomas, can cause hypoglycemia because of
binding to insulin and IGF-I receptors
• Nuclear receptor families
o Division:
§ Type 1 (GR, MR, AR, ER, PR) – bind steroids
§ Type 2 (RAR, PPAR, TR, VDR) – bind TH, VitD,
retinoic acid or lipid derivatives
o Specificity:
§ Hormone binding is usually specific for only
one type of receptor
§ Exception: GC and MC receptors
• Hormone synthesis and processing
o 1. Transcription
o 2. mRNA
o 3. Proteins
o 4. Post-translational protein processing
, o 5. Intra-cellular sorting
o 6. Membrane integration or secretion
§ POMC into ACTH
§ Proglucagon into glucagon
§ Pro insulin into insulin
§ Pro-PTH into PH
o 7. Peptide hormones are then stored into secretory granules
§ Steroid hormones diQuse into the circulation as they are produced
o 8. As these granules mature, they are poised beneath the PM for imminent
release into the circulation
o 9. The stimulating hormone is usually a releasing factor that induces rapid
changes in Ca2+ intracellular levels leading to secretory granule fusion and
release of the peptides
o 10. Degradation rate dictates the rapidity with which an hormonal signal
decays: some hormonal signals are evanescent (SST), others are long-lived
(TSH)
§ Very important for replacement therapy
o 11. In the circulation, many hormones are found couples with serum
binding proteins
§ TH4 and 3 binding to TBG, albumin an TBPA
§ Cortisol binding to CBG
§ Androgen and estrogen binding to SHBG
o 12. These interactions provide an hormonal reservoir, preventing the
otherwise rapid degradation of unbound hormones; restrict the hormones
to certain sites; and modulat the free hormone concentration
• Hormone receptors
o Membrane receptors
§ Major groups:
• GPCRs – large proteins, minerals, small peptides, aa
• TKR – insulin and other GFs
• Cytokine receptors – GH and PRL
, • Serine kinase receptors – MIS, BMPs, Gfbeta
o Nuclear receptors
§ Classification based on nature of ligands:
§ Function: mainly increasing or decreasing gene transcription
§ Location:
• Cytoplasm – GC receptors
• Nucleus – TH receptors
• Hormonal function
o Growth
§ Pathological:
• Short stature: GH deficiency, hypothyroidism, Cushing’s
syndrome, precocious puberty, malnutrition
o Maintenance of homeostasis
§ Most important ones:
• TH – controls about 25 of basal metabolism in most tissues
• Cortisol – permissive action for many hormones in addition
to its many functions
• PTH – regulates Ca2+ and PO4 levels
• Vasopressin – regulates serum osmolarity by controlling
renal free-water clearance
• MC – control vascular volume and [serum electrolytes]
• Insulin – maintains euglycemia in the fed and fasted state
o Reproduction
§ Stages of reproduction:
• 1. Sex determination during fetal development
• 2. Sexual maturation during puberty
• 3. Conception, pregnancy, lactation and child rearing
• 4. Cessation of reproductive capability at menopause
§ Hormones involved:
• LH, FSH
• Estrogen, progesterone
• Prolactin, oxytocin
• Hormonal feedback regulatory systems
o Paracrine and autocrine control
§ Paracrine – factors released by one cell that
acts on the adjacent cell in the same tissue
§ Autocrine – action of a factor on the same cell
from which it is produced
o Hormonal rhythms
§ Menstrualcycle
§ Circadian cycle
§ GnRH pulse frequency – regulating LH and FSH
secretion
• Pathological mechanisms
o Hormone excess
§ Causes:
