Thyrotropic Hormone Thyroid Stimulating Hormone (TSH)

•    Produced by basophil cells of anterior pituitary • Chemistry:

•    TSH is a dimer glucoprotein with mol. Wt. 30000

–  Consist of two subunits (α and β subunits)

–  Alpha subunit

•    Consist of 92 amino acids

•    The α-subunit of TSH, LH, FSH are nearly identical

–  Beta subunit

•   Unique from other hormones with 112 amino acids

•   Contains biological activity of thyrotropin

–  Both α and β subunits have several disulfide bonds

 

•    It also contains 21% carbohydrates linked to asparagine residues on both α and β subunits via N-glycosidic linkage

–  Two oligosaccharide chains are attached with αsubunit

–  One attached with β-subunit

•    Separately synthesized chains of α and β subunits by separate structural genes

–  Post translational modification and glycosylation

•    Regulation of TSH

•    Release is controlled by feedback mechanism

–  Thyroid hormones (T₃, T₄) inhibit it

–  TRH from hypothalamus stimulates its release

 

•    Mechanism of Action:

•    Act through glycoprotein receptors on thyroid cell membrane

–  Receptor binds to binding site on β-subunit

•    Activates adenylyl cyclase

–  cAMP is synthesized

•    Increased cAMP levels mediate its response

•    Function of TSH:

•    Stimulates the secretions of all thyroid hormones at all stages

–  Promotes iodide ion (I^-) uptake from circulation to thyroid gland

 

–  Increase the conversion of iodide (I^-) to active iodide

(I⁺) (organification)

•    Promotes the release of stored thyroid hormones

–  Increase proteolysis of thyroglobulin to release T₃ and T₄ into general circulation

•    Activates DNA contents

–  Increased production of nucleic acid and proteins and as a result cell size is increased

•    Stimulates glycolysis, TCA cycle, HMP and phospholipids synthesis with or without cAMP

•    Activates adipose tissue lipase

–  Enhance lipolysis (the release of fatty acids)

Gonadotropins

•    Influence the function and maturation of testes and ovaries

•    These include:

•    Follicle Stimulating Hormone (FSH)

•    Luteinizing Hormone (LH)

•    Human Chorionic Gonadotropin (HCG)

–  Not a pituitary hormone but a gonadotropin

•    Chemistry:

•    All these gonadotropins are glycoproteins in nature attached with

–  Sialic acid, hexose, hexosamine as carbohydrate moiety (16%)

 

•    Molecular Weight 

–  FSH: 25,000

–  LH: 40,000

–  HCG: 100,000

•    Consist of α and β subunits

–  α subunit of FSH and LH is identical to that of TSH

–  β subunit have 118 aminoacids in FSH and 112 in LH

•    Each chain have several disulfide linkages

•    A large precursor protein molecule for α and β subunits is synthesized separately in gonadotroph β cells in anterior pituitary

•    Site of synthesis of HCG is syncytiotrophoblast cells of placenta

–  Its level serves as a basis for early detect pregnancy

•    Regulation:

•    Release of FSH and LH from anterior pituitary is regulated by feedback mechanism through

–  Gonadotropin releasing Hormone (GnRH) of hypothalamus

–  Controlled by the levels of FSH and LH

•    Mechanism of action:

•    They bind to specific receptor proteins and mediate through cAMP second messenger • Metabolic Role and Biochemical Functions:

•    FSH:

•    It acts differently in males and females

•    In Females:

–  Promotes follicular growth

–  Increase the weight of ovaries

–  Prepare Graafin follicle for the action of LH

–  Enhance the production and release of estrogens from ovaries

•    In Males:

–  Promotes growth of seminal tubules

–  Stimulates testosterone production

–  Plays important role in the maturation of spermatozoa during spermatogenesis

•    Spermatogenesis

–  The formation of active, motile sperms in seminiferous tubules is stimulated by TSH

•    Luteinizing Hormone (LH):

•    In Females:

–  Causes final maturation of Graafian follicle and stimulates ovulation

•    Act synergistically with FSH and facilitate ovulation

•    Ovulatory surge is the large amount of LH secreted by pituitary during the day immediately preceding ovulation

–  Stimulate the secretions of estrogen by ovaries

–  Helps in the formation & development of corpus luteum

•    Stimulate the secretion of progesteron from corpus luteum

–  Stimulate non-germinal elements in ovary to produce androgen, and testosterons in minute amounts

 

•    In Males:

–  In males it is called as interstitial cells stimulating hormone (ICSH)

–  Stimulate interstitial cells to produce testosteron

–  Amount of testosteron secreted is proportional to the amount of LH

–  Stimulate androgen secretion

•    Development and maintenance of male secondary sex characters

•    Human Chorionic Gonadotropin (HCG)

–  Structure closely resembles with LH

–  Maintains progesteron secretion from corpus luteum during early pregnancy