Lect. 3 - Somatomammotrophic hormones Flashcards
what is somatotropin
another name for Growth hormone (GH) or somatotrophic hormone (STH)
Name 3 Somatomammotropic hormones
Growth hormone (GH) or somatotrophic hormone (STH) or somptotropin
Prolactin (PRL)
Placental lactogen (PL)
somatomammotropic hormones can also be called
somatolactotropic hormones.
The Anterior pituitary Consists of 5 main endocrine cell types
- Corticotroph
- Gonadotroph
- Lactotroph (PRL)
- Somatotroph (GH)
- Thyrotroph
what type of cell produces GH?
somatotrophs
most numerous cells of anterior
pituitary?
somatotrophs make up about 35-40% of the gland
somatotrophs are characterized by
the presence of nearly round membrane bound secretory granules
Bovine GH contains how many
amino acids?
Bovine GH contains 192 amino acids and 2 intrachain disulfide
bridges
The amino acid sequences of GH are mainly
species specific.
However, The amino acid sequences of GH in the dog and pig
are identical, being different from the cat by only one amino acid.
What species GH can effectively be
used in man to treat GH deficient children?
Only GH derived from primates can effectively be used in man to treat GH deficient children.
This is because the hGH receptor does not recognize non-primate GH. Conversely, human GH is not as
effective as bovine GH in promoting growth in cattle.
GH target tissue?
GH does not have a single target tissue.
GH acts on a variety of different tissues including liver, muscle, fat and cartilage.
GH activates a receptor associated what?
a tyrosine kinase (JAK-2)
The major action of GH is to?
promotes overall growth
(i.e. increase the rate of DNA replication, cell division and protein synthesis)
It also exerts diverse metabolic actions (usually opposite to insulin so instead of fuel uptake, it promotes fuel use).
GH’s indirect action via?
Insulin Like Growth Factors (IGF’s)
Direct metabolic actions of GH (3)
- Protein metabolism
- Lipid metabolism
- Carbohydrate metabolism
GH effect on carbohydrate metabolism?
- Decreases carbohydrate breakdown
- Increases plasma glucose levels by
inhibiting glu transport into cells & decreasing peripheral glucose utilisation.
These actions oppose those of
insulin and are considered to be
diabetogenic.
What growth is GH independent?
Growth that occurs during foetal and neonatal life is GH-independent.
GH is essential for coordinated body growth immediately after the post-natal period.
The majority of actions of GH on growth are mediated by a family of peptides known as
somatomedins (IGFs).
insulin like growth factors have another name, what is it
somatomedins (= mediators of growth)
Somatomedins (Insulin like growth factors) are Structurally very similar to
pro-insulin.
because of this structural similarity somatomedins are more frequently referred to as insulin-like growth factors (IGF’s).
two principal IGF’s have been isolated:
- IGF-I
- IGF-II
GH stimulates the synthesis of both IGF-I
and IGF-II, however one is more sensitive to GH. Which one?
IGF-I is more sensitive to GH
IGF’s can act as local hormones (at the site
of synthesis) by exerting what type of actions?
autocrine and paracrine actions.
IGF’s can also act as classical hormones (by
acting at sites distal to the site of synthesis i.e. negative feedback) to exert endocrine actions.
IGF’s bioactivity is regulated by
a family of IGF binding proteins (IGFBP)
IGF binding proteins have multiple functions:
(3)
- stabilization of circulating IGF (so increases half-life)
- delivery of IGF’s to target tissues
- local regulation (both stimulatory and inhibitory) by acting as a reservoir
IGF-1 concentrations do not fluctuate like
growth hormone concentrations
Thus IGF-1 is a good marker for growth.
In what manner is GH released?
secreted in a pulsatile manner
secretion of GH is under the control of 2
hypothalamic peptides: name them.
– Growth hormone releasing hormone
(GHRH)
– Somatostatin (SS) (GH-inhibiting hormone)
Factors which stimulate the release of GHRH from the hypothalamus include (6)
– low blood glucose
– fasting and falls in free fatty acids in blood
– increased plasma amino acids
– stress
– deep sleep
– exercise
GHRH is a smaller peptide which consists of
44 amino acids
GHRH stimulates the synthesis of
new GH by promoting transcription of GH mRNA.
- GHRH secretion is stimulated by (3)
- acetylcholine
- noradrenaline
(via alpha adrenergic receptors) - dopamine
GHRH secretion is inhibited by
adrenaline (via beta adrenergic receptors)
the “hunger hormone”
ghrelin
ghrelin contains how many amino acids
28
ghrelin is mainly produced by?
enteroendocrine cells of the gastric fundus
Ghrelin is an important stimulate of growth in what type of animal?
in young dogs, ghrelin is a more potent stimulator of GH release than GHRH is.
Somatostatin contains how many amino acids?
SS can exist as both 14 and 28 amino acid
peptides
Somatostatin (SS) is widely distributed throughout the
nervous system and is present in many extra-neural tissues including the islets of Langerhans.
Somatostatin (SS) secretion is stimulated by (2)
acetylcholine and
vasoactive intestinal polypeptide (VIP) .
Somatostatin (SS) isinhibited by
inhibited by gamma amino butyric acid (GABA)
In dogs, GH may originate from other tissue besides the adenohypophysis. What tissue?
mammary glands
GH is secreted by foci of hyperplastic ductular epithelium in mammary tissue.
In this case, GH is induced by progestins, is not pulsatile nor does it respond to GHRH or somatostatin.
deficiency of GH production in pre-pubertal animals results in
dwarfism
Three types of dwarfism of hormonal origin exist:
at the hypothalamic level
at the gland level &
at the hepatic level
Dwarfism at the hypothalamic level is due to (2)
deficiency of GHRH or excessive production of somatostatin
Dwarfism at the gland level is due to
deficiencies of GH production, even if there is sufficient GHRH present.
this glandular level is also termed primary pituitary disease.
Dwarfism at the hepatic level is due to
normal GHRH and GH levels but abnormally low IGF-1 levels, so the liver is not producing the needed IGFs adequately or at all.
in these cases, there is normal hypothalamic and pituitary function but failure to respond to GH.
e.g. Laron dwarves and African pygmies suffer from this defect).
mechanism of Laron dwarfism?
growth requires IGFs.
IGFs are bound to IGF-binding proteins.
PAPP-proteases in the body need to release IGF from the binding proteins in order for the IGFs to bind to target tissue and initiate growth.
In Laron dwarfism there is deficiency of PAPP enzyme. Thus, IGF cannot access its target.
This is called growth hormone resistance.
Hyposomatotropism aka
GH Deficiency
Can be either,
Congenital – inherited abnormality or
Aquired – injury of pituitary gland,
hypophysectomy
Congenital GH deficiency is most often encountered in what breed of dog
most often in German shepherd dogs.
but also Carelian bear dogs, Czechoslovakian wolfhound, and Saarloos wolfhound.
German shepard with pituitary dwarfinism have combined deficiency of
GH, TSH, and PRL
as well as impaired release of gonadotropins, whereas ACTH secretion is preserved.
alternative name for GH deficiency
hyposomatotropism
testing for Hyposomatotropism diagnosis is done via
Definitive: testing GH secretion – GH stimulation test.
Presumptive diagnosis
* Ruling out other causes of small stature and demonstrating low levels of IGF-1.
Rule out concurrent hypothyroidism –
thyrotropin-releasing hormone stimulation test.
Hyposomatotropism treatment principles (3)
Lack of species specific GH for therapeutic use: human and bovine GH do not work in small animals.
Alternative approach – use of progestins. Note, overtreatment can lead to acromegaly. The use of progestogens has not been considered of merit in cats.
Alternatively use pig GH. But note, GH excess can lead to diabetes mellitus.
In dogs, acromegaly is mainly due to
high progesterone levels
(due to either treatment of intact female dogs to suppress oestrus or due to endogenously high levels during dioestrus)
- progesterone induces growth of the somatotrophs which leads to an increase in GH
Acromegalic dogs are almost always female while
acromegalic cats are usually male. No known reason for this sex bias.
In cats, acromegaly is mainly due to
GH-secreting tumours (adenomas)
Acromegalic dogs are almost always female while
acromegalic cats are usually male. No known reason for this sex bias.
define Prognathism
is an extension or bulging out (protrusion) of the lower jaw (mandible). It occurs when the teeth are not properly aligned due to the shape of the face bones.
aka underbite
PRL: also called
lactogenic hormone
Prolactin (PRL) is a protein hormone. It exhibits structural homology with placental lactogen and GH.
The principal established actions of PRL are
the growth and development of mammary glands and
the initiation and maintenance of lactation post-partum.
Note that PRL has other diverse actions but the above are the principal ones.
In cattle, PRL consists of how many AAs?
199 amino acids
(human PRL also consists of 199 AAs)
What cell type produces prolactin?
PRL is synthesized by the acidophilic, lactotroph cells of the anterior pituitary
Other actions of PRL (3)
- controls the production of crop-sac milk
- promotes nest building and brood patch and feather development in certain birds
- molting in lizards
etc.
another name for prolactin inhibting hormone
dopamine
name two chemical stimulators of PRL secretion.
Vasoactive intestinal polypeptide (VIP), and
estradiol are potent stimulators of PRL
secretion.
The amount of milk secreted is dependent on
the prevailing plasma PRL concentration.
administration of L-methyl dopa (which inhibits
dopamine synthesis) results in
increased levels of PRL in the peripheral circulation
Placental Lactogen activity resembles that of
PRL rather than GH (it has little GH-like activity)
The Precise role of PL in pregnancy is unclear.
Placental Lactogen (PL) has several different actions including: (4)
lactogenic,
mammotrophic,
luteotrophic & growth promoting effects
PL has a lipolytic action and could thus provide an alternative source of energy to glycogenolysis in the mother.
