1. Anterior pituitary hormones

2. Five secretory cells producing 6 different hormones
Cortocotroph
ACTH
Gonadotroph
LH and FSH
Somatotroph GH
Lactotroph
Prolactin
Thyrotroph
TSH

3. 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

4. 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

5. Pro-opiomelanocortin
266 amino acids
Proteolytically cleaved to produce corticotrophic, opioid, and melanotrophic peptides

6. 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

7. 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

8. Action of ACTH Primary function Proper maintenance of adrenal gland
Adrenal steroidogenesis
Cholesterol transport
Conversion to pregnenolone
Inhibited by glucocorticoids

9. 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

10. 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

11. Transcription of LH beta subunit mRNA
GnRH
SF-1
Estrogen
Transcription of FSH beta
Role of GnRH and steroids
Unclear
Different promoter structure from LH

12. 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

13. Gonadal peptides Inhibins Activins Follistatin
Inhibits secretion of FSH
Activins
Stimulates FSH secretion and action
Follistatin
Inhibits FSH secretion and action

14. 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

15. 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

16. 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

17. 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

18. 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

19. Hormones Steroids Thyroid hormones
Acute elevation in glucocorticoids (+)
Chronic elevation in glucocorticoids (-)
Gonadal steroids (+)
Thyroid hormones
Inhibitory

20. Action of GH Growth and metabolism Action mediated by IGF-I
Mediation of growth
Endocrine IGF-I
Liver
Local (autocrine/paracrine) IGF-I

21. 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

22. 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

23. Post-translational modification
Glycosylation
Affects proper molecular folding
Combination of alpha and beta subunits
Regulated by TRH (+) and T3 (-)

24. Secretion of TSH Bioactivity of TSH Pulsatile secretion 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

25. Hormonal regulation Major factor of TSH secretion
Thyroid hormone concentrations
Extremely important
TRH
Dopamine (-)
Glucocorticoids (-)
SS (-)

26. Action of TSH Thyroid hormone production
G-protein coupled receptor
Thyroid cell integrity maintenance

27. Prolactin Structurally similar to GH Prolactin gene expression
Common ancestry
Chromosome 6
Prolactin gene expression
Estrogen
Dopamine
TRH
Thyroid hormones

28. Exits as monomer or polymer in circulation
23 kDa (monomer)
Most bioactive
48-56 kDa (dimer)
> 100 kDa (polymer)
Glycosylated
Less active
Binds to prolactin binding protein

29. Regulation of prolactin secretion
Inhibitory
Hypothalamic
Dopamine
Calcitonin
Paracrine factors
Endothelin-1
TGF-beta 1

30. Stimulatory
Growth factors
bFGF
EGF
Gut hormone
VIP
Estrogen

31. Function of prolactin Essential for survival Lactation Immune function
Prolactin surge during labor
Essential for initiation of lactation
Not required for maintenance of lactation
Immune function
Stimulates lymphocyte development
Reproduction
Essential for rodents