11.15.17 Growth Regulation Flashcards by Risa Beniya

Hypothalamic neurons secrete ___________, while typical neurons secrete __________. The biochemical mechanism for secretion is the same.

Hypothalamic neurons secrete hormones, while typical neurons secrete neurotransmitters.

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The hypothalamus maintains chemical/temperature homeostasis based on input. _________ and _______ state influence hormone secretion.

Emotions and metabolic state influence hormone secretion.

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Hypothalamic hormones (7)

PIH: Prolactin inhibiting hormone
PRH: Prolactin releasing hormone
TRH: Thyrotropin releasing hormone
CRH: Corticotropin releasing hormone
GHRH: Growth hormone releasing hormone
GHIH: Growth hormone inhibiting hormone
GnRH: Gonadotropin releasing hormone

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Anterior Pituitary hormones (6):

Prolactin
Thyroid stimulating hormone
Adrenocorticotropic hormone
Growth hormone
Follicle stimulating hormone
Luteinizing hormone

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Prolactin:

Simulation by ________
Inhibition by _________
Nonendocrine targets ________

Stimulation: PRH, TRH
Inhibition: PIH
Target: breast

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Thyroid Stimulating Hormone:

Stimulation by _______
Endocrine target—>hormone:

Stimulation: TRH

Endocrine target: thyroid gland —> thyroid hormones

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Adrenocorticotropic hormone

Stimulation by _________
Endocrine target—>hormones:

Stimulation by CRH

Endocrine target: Adrenal cortex —> cortisol

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Growth hormone

Simulation by _________
Inhibition by _________
Endocrine target —> hormones

Stimulation by GHRH
Inhibition by GHIH
Endocrine target —> hormones: Liver —> IGFs

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Follicle stimulating hormone, Luteinizing hormone:

Stimulation by _________
Endocrine targets —> hormones

Stimulation by GnRH

Endocrine target —> hormone: Gonadal endocrine cells —> androgens/estrogens/progesterone, gonadal germ cells

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Anterior pituitary cells and products

Corticotroph (15-20%): ACTH, beta-lipoprotein
Thyrotroph (2-5%): TSH
Gonadotroph (10-15%): LH, FSH
Somatotroph (40-50%): GH
Lactotroph (10-15%): PRL

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Growth hormone (GH, Somatotropin) stimulates secretion of ______ and ______. Regulates growth and metabolism.

Growth hormone (GH, Somatotropin) stimulates secretion of IGF-1 and IGF-2.

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Thyroid-stimulating hormone (TSH), stimulates secretion of ________ and growth of _________.

Thyroid-stimulating hormone (TSH), stimulates secretion of thyroid hormone and growth of thyroid gland.

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Adrenocorticotropic hormone (ACTH) stimulates _______ secretion by ________ and promotes growth of ______.

Adrenocorticotropic hormone (ACTH) stimulates cortisol secretion by adrenal cortex and promotes growth of adrenal cortex.

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Follicle-stimulating hormone (FSH) stimulates growth and development of _____, promotes secretion of ______ by ______. FSH is required for _____ production.

Follicle-stimulating hormone (FSH) stimulates growth and development of ovarian follicles, promotes secretion of estrogen by ovaries. FSH is required for sperm production.

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Luteinizing hormone is responsible for ovulation, _______ formation and ovarian secretion of female sex hormones. LH also stimulates cells in the testes to secrete ________.

Luteinizing hormone is responsible for ovulation, corpus luteum formation and ovarian secretion of female sex hormones. LH also stimulates cells in the testes to secrete testosterone.

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Prolactin stimulates ________ development and _____ production. Also involved in testicular function.

Prolactin stimulates breast development and milk production. Also involved in testicular function.

Growth hormone at the muscle:
____ amino acid uptake
____ protein synthesis
____ glucose uptake

Result: _____ muscle mass

Growth hormone at the muscle:
Increased amino acid uptake
Increased protein synthesis
Decreased glucose uptake (anti-insulin effect of GH)

Result: Increased muscle mass

Growth hormone at the liver:
\_\_\_\_ RNA synthesis
\_\_\_\_ protein synthesis
\_\_\_\_ gluconeogenesis
\_\_\_\_ Somatomedin production (IGF-1, IGF-2)

Growth hormone at the liver:
Increased RNA synthesis
Increased protein synthesis
Increased gluconeogenesis (anti-insulin effects of GH)
Increased Somatomedin production (IGF-1, IGF-2)

Growth hormone at the adipose:
____ lipolysis
____ glucose uptake

Result: _____ adiposity

Growth hormone at the adipose:
Increased lipolysis (anti-insulin effects of GH)
Decreased glucose uptake (anti-insulin effects of GH)

Result: Decreased adiposity

Somatomedin:
IGF-1 : primary
IGF-2 : important in fetal development

Effects in bone chondrocytes:
____ collagen synthesis
____ protein synthesis
____ cell proliferation

Results in : _____ linear growth

Effects in bone chondrocytes:
Increased collagen synthesis
Increased protein synthesis
Increased cell proliferation

Results in : Increased linear growth

Effects of somatomedins on organs and tissues:
____ RNA/DNA synthesis
____ protein synthesis
____ cell size & number

Results in : ____ tissue growth & organ size

Effects of somatomedins on organs and tissues:
Increased RNA/DNA synthesis
Increased protein synthesis
Increased cell size & number

Results in : Increased tissue growth & organ size

Overall effect of GH is to promote _______ growth and accumulation of _____ body mass.

Overall effect of GH is to promote skeletal growth and accumulation of lean body mass.

Growth hormone and somatomedins stimulate _______. Other regulators:

1) Increase by (3):
2) Decrease by (2):

Growth hormone and somatomedins stimulate somatostatin.

Other regulators:

1) Increase by (3): Exercise/stress, arginine/protein rich meal, hypoglycemia/fasting
2) Decrease by (2): High glucocorticoids, aging/obesity

Growth hormone is structurally similar to _________.

Cytokines (eg. IL-6, G-CSF)

Cytokines interact with membrane receptors of the ______ family. These receptors activate ____ tyrosine kinases that lead to phosphorylation of ______ transcription factors. The phosphorylated _____ dimerize and translocate to ______ where they turn on genes to influence cell growth and division.

Cytokines interact with membrane receptors of the cytokines receptor super family. These receptors activate JAK tyrosine kinases that lead to phosphorylation of STAT transcription factors. The phosphorylated STATs dimerize and translocate to the nucleus where they turn on genes to influence cell growth and division.

Disorders at the hypothalamus and pituitary gland are most often caused by:

Tumors

A disorder in IGF production is likely to be a result of _______ defect

``` GH receptor (Full: Laron’s dwarfism = low IGF, high GH, Partial: pygmies = low IGF-1, normal GH) ```

GH disorders at the cartilage is a result of resistance to _____

IGF-1

Typical symptoms of GH deficiency include (4):

Short stature, cherubic appearance, obesity and delayed skeletal age

Provocative testing involves (3)

Intravenous admin of insulin or arginine, used to see if patient produces expected levels of GH, if <10ng/ml = deficiency

Laron syndrome is a rare genetic mutation in the _________. It can be treated with ________.

Laron syndrome is a rare genetic mutation in the GH receptor. It can be treated with IGF-1.

Treatment for GH deficiency involves: - monitoring serum _____ levels - use until _____ are fused (puberty) or into adulthood

Treatment for GH deficiency involves: - monitoring serum IGF-1 levels - use until epiphyses are fused (puberty) or into adulthood

Four other indications for RnGH exist, name and briefly describe.

- Small for gestational age (SGA): smaller than most babies, use where there is no catch-up by age 2 - Prader-Willi syndrome (PWS): affects 1:10-15,000, short stature, polyphasic, obesity hypogonadism, mild mental retardation - Turner syndrome (PS): affects 1:2,500 girls, short stature - Idiopathic short stature (ISS): shorter than 98.8% of children, requires higher doses of GH than GH deficient patients, genetics influence dose

Recombinant IGF-1 is used for patients with ______ mutations (Laron dwarfism). Optimal dosing necessary.

Recombinant IGF-1 is used for patients with GH receptor mutations (Laron dwarfism). Optimal dosing necessary.

Sermorelin (synthetic ______) is less effective than GH, and won’t work if the defect is in pituitary production of _____.

Sermorelin (synthetic GHRH) is less effective than GH, and won’t work if the defect is in pituitary production of GH.

Hypersecretion of GH is usually due to _________. Pre-puberty, it results in ______ and post-puberty, it results in _______.

Hypersecretion of GH is usually due to pituitary tumors. Pre-puberty, it results in gigantism and post-puberty, it results in acromegaly.

GH excess can be treated with (4):

- surgery (effective in 50%) - bromocriptine (dopamine agonist) - octreotide (somatostatin analog): best, more specific at inhibiting GH than somatostatin - pegvisomant (GH receptor antagonist): peptide that binds to and prevents GH