FOLLICLE STIMULATING HORMONE(FSH), LUTEINIZING

HORMONE(LH) & TESTOSTERONE

BY: HERMAN NDJAMEN

PREVIEW 1. DEFINITION OF HORMONES2. BIOCHEMICAL CLASSIFICATION OF HORMONES3. CASE STUDIED - Structure & classification - Origin of production - Target tissues/organ(s) and functions - Mechanism of action - DISEASES

DEFINITION: Hormones are chemical substances synthesized in small amounts by endocrine tissues and carried by blood stream to another tissue, where it acts as a messenger to regulate the function of the target tissue or organ.

CLASSIFICATION OF HORMONESCLASSES OF HORMONES CHEMICAL COMPOSITION EXAMPLES

AMINO ACIDS DERIVATIVES C, H and N, AMINE GROUP CATECHOLAMINES

POLYPEPTIDES LONG CHAINS OF AMINO ACIDS INSULIN, GLUCAGON

GLYCOPROTEINS LARGE PROTEINS COMBINED WITH CARBOHYDRATES FSH, LH etc

STEROIDS LIPIDS CORTICOIDS, SEX HORMONES

FATTY ACID DERIVATIVES (EICOSANOIDS)

LONG HYDROCARBON ACID CHAINS

PROSTAGLANDINS, LEUKOTRIENES

&THROMBOXANES

CASE STUDY I: FOLLICLE STIMULATING HORMONE (FSH)

A. STRUCTURE AND CLASSIFICATION.FSH is a glycoprotein composed of 2 monomeric subunits proteins to which is attached a sugar. The dimer contains 2 polypeptides; Alpha subunit made up of 92 amino acids and a beta subunit made up of 111 amino acids. This beta subunit confers the hormone its specific biologic action and is responsible for interaction with FSH receptors. The sugar part of FSH is composed of  fucose, galactose, mannose, galactosamine, glucosamine, and sialic acidNormal level: 3mIU/ml – 10mIU/ml (million international units/ml)

ORIGIN OF PRODUCTIONThe hormone is produced in the pituitary gland(anterior) under the influence of Gonadotropic hormone releasing hormone (GnRH) produced in the hypothalamus, inhibited by inhibin and enhanced by activin. FSH is then released to the blood stream towards the target tissues. It has a plasma half life of 3-4 hours

TARGET TISSUES AND FUNCTIONS• FSH regulates the development, growth, pubertal

maturation, and reproductive processes of the human body.

• In both males and females, FSH stimulates the maturation of germ cells.

• In males, FSH induces Sertoli cells to secrete inhibin and stimulates the formation of sertoli-sertoli tight junctions (zonula occludens).

• In females, FSH initiates follicular growth, specifically affecting granulosa cells

MECHANISM OF ACTION• FSH binds to FSH-R on the cell

membrane.• This occupied receptor causes

replacement of GDP bound to Gs protein by GTP, activating this Gs protein.

• Gs alpha subunit moves to ADENYLATE CYCLASE. This cyclase then catalyzes formation of cAMP (second messenger) from ATP

• The CAMP then activates protein kinase (third messenger), which in turn by phosphorylation of cellular proteins influences on mRNA synthesis.

DISEASES1.HIGH LEVELS OF FSH• Premature menopause also known as

Premature Ovarian Failure• Poor ovarian reserve also known as Premature

Ovarian Aging• Gonadal dysgenesis, Turner syndrome (XO)• Castration• Swyer syndrome(46XY but externally female)• Certain forms of CAH• Testicular failure.• Klinefelter syndrome(XXY)

2. LOW LEVELS OF FSH

1.Polycystic Ovarian Syndrome2.Polycystic Ovarian Syndrome + Obesity + Hirsutism + Infertility3.Kallmann syndrome (incomplete puberty)4.Hypothalamic suppression5.Hypopituitarism6.Hyperprolactinemia7.Gonadotropin deficiency

CASE STUDY II: LUTEINIZING HORMONE(LH)

A.STRUCTURE AND CLASSIFICATION

LH is a heterodimeric glycoprotein. Each monomeric unit is a glycoprotein molecule; one alpha and one beta subunit make the full, functional protein. The alpha subunit is similar in all glycoprotein hormones but it’s beta subunit consists of 120 amino acids, that confers its specific biologic action and is responsible for the specificity of the interaction with the LH receptor. The carbohydrate part consist of different oligosaccharides The biologic half-life of LH is 20 minutes. During the reproductive years, typical levels of LH are between 1-20 IU/L. In males over 18 years of age, reference ranges have been estimated to be 1.8-8.6 IU/L

ORIGIN OF PRODUCTION

LUTEINIZING HORMONE is produced in the pituitary gland under the regulation of GONADOTROPIC HORMONE RELEASING HORMONE(GnRH). It is then released to the blood stream towards the target tissues

TARGET TISSUES AND FUNCTIONSIn females, LH supports theca cells in the ovaries that provide androgens and hormonal precursors for estradiol production. 

-"LH surge" triggers ovulation, thereby not only releasing the egg from the follicle, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare theendometrium for a possible implantation.

In the male, LH acts upon the Leydig cells of the testis and is responsible for the production of testosterone, an androgen that exerts both endocrine activity and intratesticular activity on spermatogenesis.

MECHANISM OF ACTION

• The mechanism of action is basically similar to that seen in FSH and the diseases observed too.

SWYER SYNDROM: HIGH FSH AND LH levels in blood.

HIGH LEVEL OF LH (low level of FSH) in female and male

CASE STUDY III: TESTOSTERONESTRUCTURE AND CLASSIFICATION

Testosterone is made up of CYCLOPENTANEPERHYDROPHENANTHRENE ring which is a characteristics of most steroid hormones. Therefore testosterone is considered to be a steroid hormone with molecular weigh (MW) = 288,4

ORIGIN OF PRODUCTION TESTOSTERONE is primarily produced in the testes by the INTERSTITIAL CELLS OF LEYDIG. Precursor of testosterone is Progesterone which is first converted to androstenedione which is then hydrolyzed to form testosterone. This is how testosterone is produced in females. Testosterone is also produced in small amount in the zona reticularis of the adrenal gland. Testosterone level is regulated by FSH and LH. LH stimulates an increase in number of leydig cells , hence increasing testosterone level, and vice versa. Testosterone is transported together with specific plasma protein binding globulin or testosterone-estrogen binding globulin

TARGET TISSUES AND FUNCTIONSTestosterone acts on several tissues of the body where it carries out the following functions:

1. It is responsible for gonadal development in the male embryo.

2. This hormone is responsible for "brain masculinization" in infant boys.

3. It is responsible for secondary sexual characteristics in male.

4. It increases energy metabolism, thereby helping men to shed extra pounds, lower their body fat, and acquire a leaner and fitter physique.

5. Testosterone is also believed to stimulate erythropoeisis

MECHANISM OF ACTION

DISEASES

• LACK OF TESTOSTERONE: this induces hypogonadism (primary- testicular failure)

• Normal level of testosterone but defective receptors induces “ testicular feminization” I.e genotype is XY but phenotype is female (swyer syndrom).

HYPOGONADISM: Deficient LH activity

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