Anterior pituitary hormones
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Anterior pituitary hormones. Five secretory cells producing 6 different hormones Cortocotroph ACTH Gonadotroph LH and FSH Somatotroph GH Lactotroph Prolactin Thyrotroph TSH. ACTH. Part of larger protein Pro-opiomelanocortin One gene (8kb, three exons and two introns)

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ACTH

  • Part of larger protein

    • Pro-opiomelanocortin

      • One gene (8kb, three exons and two introns)

        • Codes for one large protein

      • Transcription of gene

        • Activated by CRH, arginine vasopressin, cytokines

        • Inhibted by glucocorticoids


  • Transcription of POMC gene

    • CRH type 1 receptor

      • Production of cAMP and activation of protein kinase A pathway

        • Activation of CREB transcription factor

      • Activation of MAP-Kinase pathway

    • Cytokine receptor (LIF)

      • Activation of JAK/Stat pathway

        • Interaction with CRH signaling pathway


  • Pro-opiomelanocortin

    • 266 amino acids

    • Proteolytically cleaved to produce corticotrophic, opioid, and melanotrophic peptides


  • Secretion of ACTH

    • Complex regulation through HPA (hypothalamus-pituitary-adrenal) axis

    • Circadian and ultradian rhythm

      • Hypothalamic control (CRH)

        • Activity of nuclei regulated by glucocorticoids

      • Pulse amplitude rather than frequency determines circadian rhythm


Regulation of acth secretion
Regulation of ACTH secretion

  • Exercise (short and exhausting)

    • Increased secretion of ACTH

      • Hypercortisolism in athletes

  • Stress

    • Increased production of cortisol

      • Integration of information received by the CNS

      • Constrain the inflammation


Action of acth
Action of ACTH

  • Primary function

    • Proper maintenance of adrenal gland

    • Adrenal steroidogenesis

      • Cholesterol transport

      • Conversion to pregnenolone

      • Inhibited by glucocorticoids


Gonadotropins
Gonadotropins

  • Two hormones from one type of cells

    • LH and FSH

  • Glycoprotein hormones

    • Two subunits

      • Alpha

        • Universal among all glycoprotein hormones

      • Beta

        • Hormone specific

      • Combination of alpha and beta subunits

        • Essential for biological activity


Synthesis of gonadotropins
Synthesis of gonadotropins

  • Alpha subunit

    • Generated from different gene

      • Chromosome 6

    • Increased synthesis by GnRH and TRH

  • Beta subunits

    • Determinant of biological activity

      • LH beta on chromosome 19

      • FSH beta on chromosome 11



Regulation of gonadotropin secretion
Regulation of gonadotropin secretion

  • Pulsatile secretion

    • Mirror image of GnRH pulses

      • Frequency and amplitude

      • LH more sensitive to changes in GnRH

  • Gonadal steroid hormones

    • Testosterone

      • Inhibits secretion

      • Enhances FSH beta subunit mRNA transcription

    • Estrogens

      • Dual function (stimulatory/inhibitory)

      • Cyclic changes in female during reproductive cycle


  • Gonadal peptides

    • Inhibins

      • Inhibits secretion of FSH

    • Activins

      • Stimulates FSH secretion and action

    • Follistatin

      • Inhibits FSH secretion and action


Function of gonadotropins
Function of gonadotropins

  • Receptors for LH and FSH

    • Highly homologous

      • 50 % of extracellular domain

      • 80 % of transmembrane domain

  • Steroidogenesis in male and female

    • cAMP production

      • Increased cholesterol availability via increased production of steroidogenic acute regular protein (StAR)

      • Increased enzyme activity


Function of gonadotropins1
Function of gonadotropins

  • Receptors for LH and FSH

  • Steroidogenesis in male and female

    • cAMP production

      • Increased cholesterol availability via increased production of steroidogenic acute regular protein (StAR)

      • Increased enzyme activity

      • Development and function of gonadal cells and gametes

        • FSH


Growth hormone
Growth hormone

  • Human GH gene

    • Located in chromosome 17

      • 66 kb in length

      • Cluster of genes that encode closely related genes

        • GH-V

        • Placental lactogen/chorionic somatotropins

    • Transcription of GH mRNA

      • POUF1 transcription factor

        • Pituitary specificity

        • Interacts with protein kinase A pathway


  • Large polypeptide hormone

    • 191 amino acids

      • Four alpha helices looped together

  • Interacts with binding protein (GHBP)

    • Extends half-life of GH

    • Found in rodents, rabbits, and humans

      • Extracellular domain of GH receptor in human and rabbit

      • Product of alternative transcription in rodents


Regulation of gh secretion
Regulation of GH secretion

  • Major GH pulses (70 % of total daily output)

    • Slow sleep (deep sleep)

    • Age-related loss of GH

      • Decrease quality of sleep

  • Obesity and diabetes

    • Decreased GH release

    • Nutritional status

      • One of the major regulatory factor of GH secretion


  • Hormones

    • Steroids

      • Acute elevation in glucocorticoids (+)

      • Chronic elevation in glucocorticoids (-)

      • Gonadal steroids (+)

    • Thyroid hormones

      • Inhibitory


Action of gh
Action of GH

  • Growth and metabolism

    • Action mediated by IGF-I

      • Mediation of growth

      • Endocrine IGF-I

        • Liver

      • Local (autocrine/paracrine) IGF-I


  • Gender-specific pattern of GH secretion

    • Affects amount of steroidogenic enzymes

      • Gender-specific pattern of steroidogenesis

    • Gender-specific pattern of liver enzyme expression

    • Gender-specific action of GH

      • Mediated by STAT 5b activity


TSH

  • Glycoprotein hormone

    • Alpha and beta subunits

      • Alpha is identical to that of gonadotropins

      • Thyrotroph-specific expression

        • Different region of gene promoter

    • Gene for TSH beta subunit

      • Located on chromosome 1

      • Transcription regulated by Pit-1



Secretion of tsh
Secretion of TSH

  • Bioactivity of TSH

    • Glycosylation

      • Clearance rate

  • Pulsatile secretion

    • Not as pronoused as gonadotropins or GH

      • Low variation in concentrations

    • Circadian pattern

      • Increased secretion during night

        • Independent of sleep


  • Hormonal regulation

    • Major factor of TSH secretion

      • Thyroid hormone concentrations

        • Extremely important

      • TRH

      • Dopamine (-)

      • Glucocorticoids (-)

      • SS (-)


Action of tsh
Action of TSH

  • Thyroid hormone production

    • G-protein coupled receptor

  • Thyroid cell integrity maintenance


Prolactin
Prolactin

  • Structurally similar to GH

    • Common ancestry

      • Chromosome 6

  • Prolactin gene expression

    • Estrogen

    • Dopamine

    • TRH

    • Thyroid hormones



Regulation of prolactin secretion
Regulation of prolactin secretion

  • Inhibitory

    • Hypothalamic

      • Dopamine

      • Calcitonin

    • Paracrine factors

      • Endothelin-1

      • TGF-beta 1


  • Stimulatory

    • Growth factors

      • bFGF

      • EGF

    • Gut hormone

      • VIP

    • Estrogen


Function of prolactin
Function of prolactin

  • Essential for survival

    • Lactation

      • Prolactin surge during labor

        • Essential for initiation of lactation

      • Not required for maintenance of lactation

    • Immune function

      • Stimulates lymphocyte development

    • Reproduction

      • Essential for rodents


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