Pituitary and Gonadal Hormones Flashcards
What is the master endocrine gland in the body?
Pituitary gland
What does it mean if the pituitary gland is in hypophysis?
Rests at the base of the brain
What is the pituitary gland connected to?
Hypothalamus by a stalk of neurosecretory fibers and blood vessels
Where is the pituitary gland located? (2)
Anterior and posterior lobes
The pituitary gland secretes hormones to control what? (3)
Growth
Metabolism
Reproduction
What does the hypothalamic neurosecretory cells produce?
These get transported to the pituitary gland by what?
These peptides do what?
Releasing or inhibitory hormones
Portal venous system
Stimulate or inhibit release of hormones from the anterior pituitary gland
What is synthesized in the hypothalamus and where are they transported?
Vasopressin/ADH and oxytocin
Posterior pituitary lobe
8 hypothalamic hormones?
- GHRH : Growth hormone releasing hormone
- TRH : Thyrotropin releasing hormone
- CRH : Corticotropin releasing hormone
- GnRH : Gonadotropin releasing hormone
- No PRL (Prolactin) releasing hormone
- Dopamine
- Somatostain (SST)
- Vasopressin/ADH and Oxytocin
Pituitary cell AND hormone of GHRH?
Somatotropes
Growth hormone/Somatotropin
Pituitary cell AND hormone of TRH?
Thyrotropes
Thyroid stimulating hormone (TSH)
Pituitary cell AND hormone of CRH?
Corticotropes
Adrenocorticotropin (ACTH)
Pituitary cell AND hormone of GnRH?
Gonadotropes
Follicle stimulating hormone (FSH) and leuteinizing hormone (LH)
Pituitary cell AND hormone of No PRL?
Lactotropes
Prolactin (PRL)
Pituitary cell AND hormone of DA?
Lactotropes
Inhibits release of PRL
Pituitary cell AND hormone of SST?
Somatotropes
Inhibits release of GH
Pituitary cell AND hormone of Vaso/ADH and Oxy?
N/A (made in hypo)
Vasopressin and Oxytocin are stored in posterior pituitary
What type of cell are somatotropes and lactotropes?
acidophilic cells
What type of cell are corticotropes?
Basophilic cells
What type of cell are thyrotropes and gonadotropes?
basophilic or chromophobic cells
Where are hormones stored?
Secretory granules
Somatotropin (Growth Hormone) is required for what?
What type of binding site does it have?
Effects are mediated by ______ and ______
Normal growth during childhood and adolescence
Two GH receptor binding sites
Jak/Stat and IGF1
Half life of somatotropin is ______
After the half-life it is released where? what does it bind to?
20-25minutes
Released into circulation
Binds to GH binding protein (GHBP)
Recombinant GH half-life?
36h
Action of Growth Hormone in adipose? (3)
Increases lipolysis
free FA production
decrease glucose uptake
Action of Growth Hormone in muscle? (2)
Increases protein synthesis and decreases glucose uptake
Action of Growth Hormone in Liver? (1)
Increase IGF-1 synthesis
What is the storage form of IGF in the blood?
IGF-1/IGF binding protein/acid labile subunit complex
GH deficiency leads to what? (3)
What is the cause of GH deficiency? (2)
Failure to reach normal height
Increased body fat
Decreased lean mass
Genetic causes or damage to pituitary gland or hypothalamus
What is essential for normal prenatal and postnatal growth?
IGF-1
What is a long-acting formulation of GH done in different trials to study GH deficiency?
PLA/hGH complex
Therapeutic uses of recombinant GH? (8)
Growth failure in dwarfism Prader-Willi syndrome Noonan syndrome Turner syndrome Wasting in AIDS Short bowel syndrome Anti-aging programs Athletes
Side of effects of GH therapies?(4)
Increased activity of CYP450 isoforms
Edema
Myalgia
Arthralgia
Example of a recombinant IGF-1 drug?
It’s used to treat what?
Mecasermin
Treat children with severe IGF-1 deficiency and patients with mutations in genes for GH receptor, signaling components, antibodies to GH and IGF-1 gene defects
Two forms of recombinant IGF-1 approved by FDA?
Mecasermin (rhIGF1) Mecasermin rinfabate (complex of rhIGF1 and rhIGF binding protein 3)
Adverse side effects of mecasermin? (2)
Hypoglycemia
Intracranial hypertension
GH antagonists are used to treat patients with what? This problem leads to ____
When does the problem cause gigantism?
GH producing adenomas
Acromegaly
When adenomas occur before closure of epiphyseal plate of the long bones
Small GH secreting adenomas can be treated with __________ and __________
Large GH secreting tumors are treated with ______ or ________
Somatostatin
GH receptor antagonists
Surgery or radiation
Somatostatin inhibits release of what? (5)
What is 45x more potent that SST in inhibiting GH release but 2x as potent in reducing insulin secretion?
GH, TSH, glucagon, insulin, gastrin
Octreotide
Example of a GH receptor antagonist? It is used to treat _______
Where does it bind?
It allows ______ but it blocks what?
Pegvisomant
Acromegaly
Binds to 2 GH receptor sites, one with increased affinity and one with reduced affinity
Allows receptor dimerization but blocks conformational changes needed for signal transduction
What is a protein nearly identical to LH that acts through LH receptors?
It regulates the production of what?
Human chorionic gonadotropin (hCG)
Progesterone during pregnancy
In women, FSH and LH are required for what?
FSH : follicular development in ovaries
LH: ovulation
Both: ovarian steroid hormone production
In men, FSH regulates ____________ from which cells?
LH stimulates synthesis of __________ in which cells?
Spermatogenesis from Sertoli cells
Testosterone in Leydig cells
FSH, LH and hCG share which two subunits?
What are the recombinant forms?
These are used to treat what? (3)
alpha and beta
FSH (follitropin alpha, follitropin beta), LH (leutropin alpha), hCG (chorionic gonadotropin alpha)
Infertility, assisted reproductive technologies and superovulation for transgenics
TSH regulates levels of secretion of what (2) from the thyroid gland?
These can in turn inhibit the secretion of ____ and ____ synthesis
Thyroid hormone (T3 and T4) TRH and TSH
Is TSH usually used as a therapeutic preparation?
No
Name for T4? It treats what?
Levothyroxine
Hypothyroidism
Adrenocorticotropic hormone (ACTH) works on the ______ ____ and releases hormones
adrenal cortex
ACTH’s major glucocorticoid is ______. It’s roles include ____ and _____
Cortisol
Immune function and intermediary metabolism
ACTH’s major mineralocorticoid is _______ and play a role in which activity?
Aldosterone
Salt-retaining activity
Prolactin stimulates production of what? (5)
Milk Estrogens Progestins Corticosteroids Insulin
Is prolactin deficiency common?
Are PRL preparations available for treatment of deficiencies?
No, rare
No
Elevated levels of prolactin could be due to what? (3)
PRL secreting adenomas
damage to hypothalamus
impaired transport of dopamine
Disease related to prolactin?
What is the treatment?
Hyperprolactinemia
Dopamine agonists
Role of dopamine in regard to PRL?
Inhibits secretion PRL from anterior pituitary
2 dopamine agonists? What do they do?
Bromocriptine
Cabergoline
Bind dopamine D2 receptors in lactotropes and decrease PRL release
Oxytocin participates in what? (3)
Labor
Uterine contractions
Milk ejection in lactating women
Oxytocin acts through which receptor? and which second messenger system?
G protein coupled receptor
Phosphoinositide-calcium second messenger system
Drug that acts on oxytocin? What type of drug is it? What does it treat?
Is it approved by the FDA?
Atosiban
Oxytocin receptor antagonist
Treats preterm labor (tocolysis)
No
Vasopressin is released from posterior pituitary in response to what?
Failing blood pressure
Vasopressin activates two types of ______
GPCRs
Vasopressin mediates vasoconstriction via which receptor?
Increases water reabsorption via which receptor?
V1
V2
Vasopressin deficiency leads to which disease?
Diabetes insipidus
Drug that is a synthetic analog of vasopressin?
Desmopressin
Inappropriate secretion of vasopressin causes increase in ______ and lowers ______
Blood volume
Blood sodium
Two vasopressin antagonists? affinity for which vasopressin receptors?
Conivaptan (affinity for V1 and V2)
Tolvaptan (higher affinity for V2 rather than V1)
ACTH is typically used to diagnose what disease?
Adrenal insufficiency
