2B Hypothalamus & Pituitary review

What organ is considered the “master regulator” of the endocrine system? Why?

Hypothalamus, links the nervous and endocrine systems.

How is the hypothalamus connected to the pituitary?

Pituitary stalk

What does the pituitary stalk contain?

Blood vessels & axons of neurons

What are the two regions of the pituitary? What types of cells are present in those regions?

Adenohypophysis (anterior) - vascular connection containing endocrine cells

Neurohypophysis (posterior) - neural connection, consists of neurons

What specialized vascular structure connects the hypothalamus and the anterior pituitary?

Portal system

What is the physiological benefit from the portal system?

Hypothalamic hormones only have to travel a short distance, ideal for their short half-lives (short peptide hormones).

What controls the secretion of hypothalamic hormones?

Neural signals and hormone feedback signals

Are hypothalamic hormones stimulators or inhibitory?

Both

What controls secretion of anterior pituitary hormones?

Hypothalamic regulatory hormones

Are hormones from the anterior pituitary stimulatory or inhibitory?

Stimulatory

What six major hormones are made by the hypothalamus?

GnRH, CRH, TRH, Dopamine, GHRH, Somatostatin

Which hypothalamic hormones are considered stimulatory?

GnRH, CRH, TRH, GHRH

Which hypothalamic hormones are considered inhibitory?

Dopamine, Somatostatin

Corticotrophin-releasing hormone (CRH) is a …

41 AA polypeptide

CRH is secreted in a …

Diurnal (daily) pattern

Peak occurs in the early AM

CRH binds to which receptor in which organ?

Corticotrophin-releasing hormone receptor(CRH-R1) in the anterior pituitary gland

CRH-R1 is expressed in which cell type of the anterior pituitary gland?

Corticotrophs

CRH-R1 is what kind of receptor? How does its activation affect target cells?

Gs-Linked GPCR that stimulated both POMC transcription & release

What enzyme cleaves POMC into several bioactive peptides?

Prohormone convertases

What are the products of POMC cleavage?

Corticotropin (ACTH)

What is the structure of adrenocorticotropic hormone (ACTH)?

39 AA poly peptide

ACTH is secreted in a …

Diurnal (daily) pattern

Follows CRH peak in early AM

How is ACTH transported in circulation?

50% free, 50% protein-bound (conticotropin-binding globulin)

What is the half-life of ACTH?

Short (~10 min)

To what receptor does ACTH bind? Where?

Melanocortin-2 receptor (MC2R) on adrenal cortical cells

MC2R is what kind of receptor? How does its activation affect target cells?

Gs-linked GPCR that stimulates glucocorticoid (cortisol) production.

Thyrotropin-releasing hormone (TRH) is a …

3 AA peptide hormone

TRH binds to what receptor, organ, cell type?

Thyroptin-releasing hormone receptor (TRHR) on thyrotrophs in the anterior pituitary.

TRHR is what kind of receptor? How does its activation affect target cells?

Gq-linked GPCR that stimulates synthesis and release of TSH

Is TRH the only hormone controlling TSH release

No, Somatostatin (SS)

What kind of receptor is the SS receptor? How does its activation affect target cells?

Gi-linked GPCR that inhibits thyrotroph secretion of TSH

What glycoprotein hormones are made by the anterior pituitary gland?

TSH, FSH, LH

What does “glyco” refer to?

The glycosylation of the glycoproteins, increasing both half-life and receptor affinity.

Glycoprotein hormones consist of …

Alpha & beta subunits which are noncovalently linked

Which glycoprotein subunit confers receptor specificity?

The beta subunit, unique to each hormone.

Alpha subunit is identical across all glycoproteins.

Why do half-lives differ between glycoproteins?

Difference in glycosylation

Thyroid stimulating hormone (TSH) is a …

112-118 AA glycoprotein

TSH is produced by …

Thyrotrophs

Where are TSH receptors expressed?

Thyroid follicular cells

What kind of receptor is TSHR? How does its activation affect targeted cells?

Gs-linked GPCR, stimulates thyroid hormone production (T3 & T4).

What is the structure of gonadotrophin-releasing hormone (GnRH)

10 AA polypeptide

To what receptor does GnRH bind, where?

Gonadotrophin-releasing hormone receptor (GnRHR) on gonadotrophs

What kind of receptor is GnRHR? How does its activation affect target cells?

Gq-linked GPCR that stimulates the synthesis and release of FSH and LH

How is GnRH released, why?

Pulsating manner, helps prevent GnRH receptor downregulation

How can you increase LH and FSH release?

Increase GnRH pulse frequency

How are FSH and LH stored within gonadotrophs?

In speperate secretory vesicles

How are FSH and LH secreted, why?

Pulsating manner because GnRH is secreted in the same manner.

What is the target organ of the gonadotropins?

Gonads (ovaries & testes).

What receptors do LH and FSH bind in the gonad? What type of receptors are they?

-FSH binds FSHR (Gs-linked GPCR)

-LH binds LHCGR (Gs-linked GPCR)

What are chorionic gonadotropins, and how does its they differ from pituitary gonadotropins?

Related family members produced by the placenta & are not regulated by the hypothalamus/pituitary.

What are the chorionic gonadotropins and what receptors do they bins?

Equine chorionic gonadotropin (eCG) - binds FSHR (primarily) & LHCGR, has a ~ 3-5 day half-life

Human chorionic gonadotropin (hCG) - binds LHCGR, with a half-life of 24 h.

What kind of hormone is dopamine (DA)?

Catechomaline

What receptor does DA bind? Where is this receptor expressed?

Dopamine receptor 2 (D2 receptor) on lactotrophs.

What type of receptor is the D2 receptor? What is the result of receptor activation?

Gi-linked GPCR that inhibits prolactin (PRL) release.

How can prolactin (PRL) secretion be stimulated?

TRH & some GI hormones

What kind of hormone is prolactin (PRL)?

Somatomammotropin

199 AA single-chain protein with three disulfide bonds

Why do PRL and GH have some overlap in their biological activities?

50% homologous between protein sequences.

What cells synthesize PRL & how is synthesis regulated?

Produced on lactotrophs, inhibited by activation of D2 receptor.

How is PRL transported in circulation, and what is its half-life?

50% free & 50% protein-bound

Short half-life (~20 min)

What receptor does PRL bind? Where is this receptor expressed?

PRL receptor on a variety of cells; major target organ is the mammary gland.

What is the receptor type & what is the result of activation of the PRL receptor?

Cytokine receptor utilizing the JAK-STAT signaling pathway, primary role in lactation

What kind of hormone is GHRH?

44 AA polypeptide

What receptor does GHRH bind? Where is this receptor expressed?

Growth hormone releasing hormone receptor (GHRHR) on somatotrophs

What type of receptor is GHRHR and what is the result of receptor activation?

Gs-linked GPCR that stimulated GH gene transcription & secretion

What kind of hormone is somatostatin (SS)?

14 AA polypeptide

What receptor does SS bind? Where is this receptor expressed?

Somatostatin receptor on somatotrophs

What receptor type is somatostatin receptor & what is the result of receptor activation?

Gi-linked GPCR that inhibits GH secretion

What kind of hormone is GH?

somatomammotropin

191 AA single-chain protein with three disulfide bonds

What cells synthesize GH & how is synthesis regulated?

Produced by somatotrophs, stimulated by GHRHR activation; inhibited by SS

How is GH transported in blood?

50% free & 50% protein-bound (GH-binding protein)

What receptor does GHRH bind bind? What type of receptors is this?

GH receptor on a variety of cells (mainly liver)

Cytokine receptor utilizing the JAK-STAT signaling pathway

Which Somatomammotropin is part of an endocrine axis? Why?

GH

IGH-1 provides negative feedback

What kind of hormone is IGF-1?

70 AA polypeptide

What type of receptor does IGF-1 bind to?

IGF-1 receptor (IGF-1R)

Receptor tyrosine kinase

How does GH directly mediate its function?

Direct GH actions are mediated via GH receptor

Which cells/tissues ONLY express GH receptors?

Adipocytes, hepatocytes

How does GH alter cellular function?

Increased lipid metabolism for energy.

Increased carbohydrate synthesis (gluconeogenesis)

Decreased glucose uptake

Increased IGF-1 production (liver)

How does GH mediate its indirect effects?

Indirect actions of GH are mediated via IGF-1

Which cells/tissues express both GH & IGF-1 receptors?

Myocytes, chondrocytes, visceral organs

How do GH & IGF-1 alter cellular function?

Decreased carbohydrate metabolism

Increased protein/DNA/RNA synthesis

Increased cell proliferation &/or hypertrophy

Which situations are associated with increased GH release?

Neurogenic & physical stress

Starvation/fasting

Exercise

Hypoglycemia

Presence of certain AAs in serum

Estrogen/testosterone

Thyroid hormone

Which situations are associated with decreased GH release?

Obesity

Hyperglycemia

Increased free fatty acids in serum

What is the cause of dwarfism?

Hyposomatotropism (GH deficiency)

is disproportionate dwarfism related to GH?

No, chondrodysplasia is abnormal growth of cartilage

What is the effect of excess GH exposure?

Hypersomatotropism

Clinical signs: enlarged head, heart, liver, kidneys, and thickened skin.

Why would you administer exogenous GH?

Treatment for dwarfism

Recombinant bovine somatotropin (bovine GH) to increase milk production