Enrico Tiepolo
Endocrine System
Many functions of the organism are regulated by hormones, i.e. chemical mediators that are secreted by
specific organs (glands) or tissue into the bloodstream, after a specific stimulus.
Remember:
• Endocrine organs = release hormones into the bloodstream
• Exocrine organs = release (various) secretions to the exterior of the organism/interstice to influence
surrounding cells (paracrine action) or themselves (autocrine action)
• Some hormones, like ADH (vasopressin), are secreted by neurons of the hypothalamus and in
this case, we talk about neurosecretion: the boundaries between neurotransmitters and
hormones have become labile.
• Action of hormones is sensed by tissues/cells that possess appropriate receptors
• Same hormone may bind to different receptor and therefore have different actions: different
receptor may imply different transduction cascade
• Hormones act at distance à they are NOT labile substances (e.g. prostaglandins, paracrine
fashion). They are tyrosine or tryptophan derivatives, peptides or steroidal derivatives of
cholesterol
Hormones classification
Peptides hormones:
• biggest family
• include very small peptides e.g., TRH (3 amino acids)
• but also polypeptides e.g., insulin and FSH
Aminic hormones:
• e.g., thyroid secreted hormones and tyrosine derivatives hormones à T3 and T4 and
catecholamines
• e.g., melatonin derived by tryptophan
Steroidal hormones:
• e.g., aldosterone, cortisol, sex hormones
Moreover, some substances possess a hormonal function but localized such as leukotrienes, thromboxane
and prostaglandins.
An “endocrine system” can be identified in the body, as a set of endocrine organs and tissues, whose
main function is to produce and release hormones under control of specific signals. The coordination
center of the latter system consists in the axis that the hypothalamus and the hypophysis create.
However, many other tissues in the body exert an endocrine action, in response to local stimuli/
autonomic nervous system.
Tissues and organs belonging to the endocrine system:
• Hypothalamic-pituitary axis
• Pineal gland: melatonin (ß sympathetic control of the superior cervical ganglion, under the
suprachiasmatic nucleus and paraventricular of the hypothalamus)
• ! #$% & Langerhans islets: glucagon and insulin (ß abnormal glycemia)
• G cells of the gastric antrum: gastrin (ß high aminoacid content in the lumen)
• Duodenal cells: secretin and cholecystokinin (CCK) (ß receiving gastric content)
o Secretin: secretion of water and bicarbonate by pancreas
o CCK: release of bile by gallbladder + secretion of digestive enzymes by pancreas
• Right atrium cells: atrial natriuretic peptides (ANP) (ß increased distension = excess volume of
plasma and body fluid à more fluid in the body) [Opposite signal of aldosterone/ angiotensin
which accumulated body fluid]
• Juxtaglomerular cells in the kidneys: renin (ß paracrine prostaglandins release by macula densa)
Major organs of the endocrine system are instead the thyroid, the adrenal cortex of the adrenal glands
and the gonads. These organs receive inputs from the pituitary gland, which releases tropins to control
2 Body At Work II
, Enrico Tiepolo
them. The pituitary gland is not the only regulation they are under: in fact, they possess receptors that
act as negative feedback control for their own hormone secretion.
The tropins also have a trophic effect on the target tissues and are released by distinct populations
of pituitary cells that are therefore called thyrotrophs, corticotrophs, gonadotrophs. These are in turn
stimulated or inhibited by specific hypothalamic factors, and the responsible neurons in the
hypothalamus are generally subject to negative feedback control by the downstream
hormones.
As a consequence, the lack of triiodothyronine (T3, the thyroid hormone) will produce high levels of the
thyrotropin releasing hormone (TRH, by the hypothalamus) and of thyrotropin (thyroid stimulating
hormone, TSH, by the hypophysis), whereas a thyroid tumor secreting T3 will determine low levels of
TRH and TSH. A similar story can be told for corticotropin releasing hormone (CRH), corticotropin
and cortisol: high cortisol may be associated to low CRH and low corticotropin (adrenal tumor)/ to low
CRH and high corticotropin (pituitary tumor) and high cortisol.
This concept of there being both a short and a long feedback control loop in the endocrine axis
clearly is clinically important in diagnosing the source of an altered hormonal level.
Receptors and transcriptions cascades
1)On GPCRs act catecholamines and some peptide hormones.
Mainly have effects on the biochemical paths but can also trigger transcription of “early” or
“late” genes.
Hypothalamic factors that generally act on GPCRs:
• GHRH – growth hormone releasing hormone and CRH – corticotropin releasing hormone.
Activation of Gs coupled receptors à cAMP à PKA à phosphorylation of target proteins +
transcription of GH gene or gene for pro-opio-melanocortin (POMC) (pro-hormone for which
corticotropin and melanocyte stimulating hormone MSH are produced).
• SRIF – somatostatin releasing hormone (also called growth hormone inhibiting hormone),
opposite role with respect to GHRH
Activation of Gi à opposite effect of Gs
• TRH – thyrotropin releasing hormone favors both the transcription of thyrotropin and vesicle
release, via activation of Gq coupled receptors à Phospholipase C à IP3, DAG à PKC à
Phosphorylation of target proteins
Exceptions:
• ANP receptor which creates cGMP
• Angiotensin 2 which in some tissues can activate PLA2 (Phospholipase A2), inducing the
release of AA (arachidonic acid).
2) On Receptor Tyrosine Kinases (RTKs) act peptide hormones.
Act on the tyrosine kinase cascades and eventually phosphorylate, relocate in the nucleus and
thus activate transcription factors. They can also interfere with biochemical paths (non-
transcriptional effects).
3 Body At Work II
Endocrine System
Many functions of the organism are regulated by hormones, i.e. chemical mediators that are secreted by
specific organs (glands) or tissue into the bloodstream, after a specific stimulus.
Remember:
• Endocrine organs = release hormones into the bloodstream
• Exocrine organs = release (various) secretions to the exterior of the organism/interstice to influence
surrounding cells (paracrine action) or themselves (autocrine action)
• Some hormones, like ADH (vasopressin), are secreted by neurons of the hypothalamus and in
this case, we talk about neurosecretion: the boundaries between neurotransmitters and
hormones have become labile.
• Action of hormones is sensed by tissues/cells that possess appropriate receptors
• Same hormone may bind to different receptor and therefore have different actions: different
receptor may imply different transduction cascade
• Hormones act at distance à they are NOT labile substances (e.g. prostaglandins, paracrine
fashion). They are tyrosine or tryptophan derivatives, peptides or steroidal derivatives of
cholesterol
Hormones classification
Peptides hormones:
• biggest family
• include very small peptides e.g., TRH (3 amino acids)
• but also polypeptides e.g., insulin and FSH
Aminic hormones:
• e.g., thyroid secreted hormones and tyrosine derivatives hormones à T3 and T4 and
catecholamines
• e.g., melatonin derived by tryptophan
Steroidal hormones:
• e.g., aldosterone, cortisol, sex hormones
Moreover, some substances possess a hormonal function but localized such as leukotrienes, thromboxane
and prostaglandins.
An “endocrine system” can be identified in the body, as a set of endocrine organs and tissues, whose
main function is to produce and release hormones under control of specific signals. The coordination
center of the latter system consists in the axis that the hypothalamus and the hypophysis create.
However, many other tissues in the body exert an endocrine action, in response to local stimuli/
autonomic nervous system.
Tissues and organs belonging to the endocrine system:
• Hypothalamic-pituitary axis
• Pineal gland: melatonin (ß sympathetic control of the superior cervical ganglion, under the
suprachiasmatic nucleus and paraventricular of the hypothalamus)
• ! #$% & Langerhans islets: glucagon and insulin (ß abnormal glycemia)
• G cells of the gastric antrum: gastrin (ß high aminoacid content in the lumen)
• Duodenal cells: secretin and cholecystokinin (CCK) (ß receiving gastric content)
o Secretin: secretion of water and bicarbonate by pancreas
o CCK: release of bile by gallbladder + secretion of digestive enzymes by pancreas
• Right atrium cells: atrial natriuretic peptides (ANP) (ß increased distension = excess volume of
plasma and body fluid à more fluid in the body) [Opposite signal of aldosterone/ angiotensin
which accumulated body fluid]
• Juxtaglomerular cells in the kidneys: renin (ß paracrine prostaglandins release by macula densa)
Major organs of the endocrine system are instead the thyroid, the adrenal cortex of the adrenal glands
and the gonads. These organs receive inputs from the pituitary gland, which releases tropins to control
2 Body At Work II
, Enrico Tiepolo
them. The pituitary gland is not the only regulation they are under: in fact, they possess receptors that
act as negative feedback control for their own hormone secretion.
The tropins also have a trophic effect on the target tissues and are released by distinct populations
of pituitary cells that are therefore called thyrotrophs, corticotrophs, gonadotrophs. These are in turn
stimulated or inhibited by specific hypothalamic factors, and the responsible neurons in the
hypothalamus are generally subject to negative feedback control by the downstream
hormones.
As a consequence, the lack of triiodothyronine (T3, the thyroid hormone) will produce high levels of the
thyrotropin releasing hormone (TRH, by the hypothalamus) and of thyrotropin (thyroid stimulating
hormone, TSH, by the hypophysis), whereas a thyroid tumor secreting T3 will determine low levels of
TRH and TSH. A similar story can be told for corticotropin releasing hormone (CRH), corticotropin
and cortisol: high cortisol may be associated to low CRH and low corticotropin (adrenal tumor)/ to low
CRH and high corticotropin (pituitary tumor) and high cortisol.
This concept of there being both a short and a long feedback control loop in the endocrine axis
clearly is clinically important in diagnosing the source of an altered hormonal level.
Receptors and transcriptions cascades
1)On GPCRs act catecholamines and some peptide hormones.
Mainly have effects on the biochemical paths but can also trigger transcription of “early” or
“late” genes.
Hypothalamic factors that generally act on GPCRs:
• GHRH – growth hormone releasing hormone and CRH – corticotropin releasing hormone.
Activation of Gs coupled receptors à cAMP à PKA à phosphorylation of target proteins +
transcription of GH gene or gene for pro-opio-melanocortin (POMC) (pro-hormone for which
corticotropin and melanocyte stimulating hormone MSH are produced).
• SRIF – somatostatin releasing hormone (also called growth hormone inhibiting hormone),
opposite role with respect to GHRH
Activation of Gi à opposite effect of Gs
• TRH – thyrotropin releasing hormone favors both the transcription of thyrotropin and vesicle
release, via activation of Gq coupled receptors à Phospholipase C à IP3, DAG à PKC à
Phosphorylation of target proteins
Exceptions:
• ANP receptor which creates cGMP
• Angiotensin 2 which in some tissues can activate PLA2 (Phospholipase A2), inducing the
release of AA (arachidonic acid).
2) On Receptor Tyrosine Kinases (RTKs) act peptide hormones.
Act on the tyrosine kinase cascades and eventually phosphorylate, relocate in the nucleus and
thus activate transcription factors. They can also interfere with biochemical paths (non-
transcriptional effects).
3 Body At Work II
