Animal Science 434Reproductive Physiology

Lecture 6 and 7: Endocrinology

What is the function of the endocrine system?

Integration of Body Functions

• nervous and endocrine systems are similar

• nervous system» seconds

• endocrine system» minutes and hours

Neuro-endocrine Response

Manipulation of the Endocrine System

• Hormones can be used to regulate body functions»growth (anabolic steroids)

» lactation (GH or STH)

»birth control (Estradiol, Progesterone)

»estrous cycle (PGF2)

»superovulation and embryo transplant (FSH,eCG)

»parturition (oxytocin)

Endocrine Gland

• A ductless gland• Secretes substances (hormones) into

blood or lymph that affect cells elsewhere in the body

• The secretion does not involve loss of tissue

Exocrine Gland

• A gland with ducts that are used for secretion

Hormone

• Substance produced by endocrine gland

• Acts on cells, tissues or organs at a place other than where produced

• Acts as a catalyst.

Testes(in bull)

Placenta

Uterus

OvaryAdrenalPineal

Hypothalamus

Pituitary

Pancreas

Thyroid

Endocrine Glands

Classification and Properties of Hormone

A. Site of Production

B. Type of action

1. Primary hormone of reproduction

2. Metabolic hormone

C. Chemical Structure

1. General structure– Proteins and polypeptides

– Steroids

– Fatty acids

– Modified amino acid

2. Size

Classification and Properties of Hormone

A. Site of Production

B. Type of action

1. Primary hormone of reproduction

2. Metabolic hormone

C. Chemical Structure

1. General structure– Proteins and polypeptides

– Steroids

– Fatty acids

– Modified amino acid

2. Size

Location of the Hypothalamus and Pituitary Gland

Hypothalamus

Function of Hypothalamus• appetite

• thirst

• body temperature

• vasomotor activity

• emotion

• use of body nutrient reserves

• activity of intestine

• sleep

• sexual behavior

• Production and release of releasing hormones

Releasing Hormones of the Hypothalamus

A. Structure

• short chain polypeptides (3 - 44 amino acids)

B. General Function• to cause the release of trophic hormones from

the anterior pituitary gland

Releasing Hormones of the Hypothalamus

C.Hormones

•Gonadotropin releasing hormone (GnRH)

»LH, FSH release

•Thyrotrophin releasing hormone (TRH)

»TSH and prolactin release

•Corticotrophin releasing hormone (CRH)

»ACTH release

•Growth hormone releasing hormone (GH-RH)

•Somatostatin (growth hormone inhibiting hormone)

Hypothalamus

Cells of the Anterior Pituitary

• LH• FSH• Prolactin• STH• TSH• ACTH

HypothalamusHypothalamus

Nerve CellsNerve Cells

Superior hypophyseal

artery

Hypophyseal portal vessels

Capillary plexus

Posterior pituitary

Capillary plexus

Preoptic nuclei

cell

Preoptic nuclei

cell

Anterior Pituitary Hormones

A.Structure1. glycoproteins or proteins

B.Hormones1. gonadotropins

» Follicle stimulating hormone (FSH)

» Luteinizing hormone (LH)

» Prolactin

Anterior Pituitary Hormones

2.Other trophic hormones•Adrenal Corticotropin (ACTH)

• thyroid stimulating hormone (TSH)

•growth hormone (GH or STH)

Structure of LH, FSH and TSH

• Made of 2 amino acid chains

• chains are the same

• chains differ and give specificity

S S

HypothalamusHypothalamus

Nerve CellsNerve Cells

Posterior pituitary• Oxytocin• ADH

Paraventricular nuclei cell

Paraventricular nuclei cell

Supraoptic nuclei cellSupraoptic nuclei cell

Anterior Pituitary

Capillary plexus

Hypothalamus

Nuclei that produce posterior pituitary

hormones

Nuclei that produce posterior pituitary

hormones

Posterior Pituitary HormonesA.Structure

• polypeptides (9 amino acids)

B. Hormone

• Oxytocin - contraction of smooth muscle

Placental Hormones

• Equine Chorionic Gonadotropin (eCG)» Formation of accessory CL and maintains

pregnancy

• Human Chorionic Gonadotropin (HCG)» Maintains primate CL and pregnancy

• Placental Lactogen (PL)» Development of the mammary gland in

the mother

• Steroids - Estrogen and Progesterone

Gonadal Polypeptide Hormones

• Relaxin» Secreted by CL during pregnancy.

» Parturition

• Inhibin» Inhibits FSH release

Gonadal Steroids

A. General» Origin - ovary, testis, adrenal

» Structure

2

3

4

5

10

1

6

7

8

9 14

13

12

11

15

16

17

19

18

20

DC

BA

SteroidSynthesis

HO

OH

O

OH

HO

CH3

C O

O

CH3

C O

HO

Cholesterol Pregnenolone

Estradiol

ProgesteroneTestosterone

27-C27-C

21-C21-C

19-C19-C

18-C18-C

21-C21-C

Gonadal Steroids Cont.A.General Cont.

» Solubility– Bound to a binding protein for transport

B.Type of Steroids» Androgens - Testosterone

» Estrogen - Estradiol

» Progestin - Progesterone

SteroidSynthesis

HO

OH

O

OH

HO

CH3

C O

O

CH3

C O

HO

Cholesterol Pregnenolone

Estradiol

ProgesteroneTestosterone

MitochondriaMitochondria

Smooth ERSmooth ER

Other Hormones

A.Prostaglandins1. PGF2

Lipid Hormones - ProstaglandinsFatty AcidsProstaglandins

1. Produced by all tissues of body2. Can have a local effect on tissues (same tissue which produced it)3. Rapidly degraded in lungs

Phospholipids- Rate limiting (Phospholipase A2)

- Precursor to Prostaglandins

Aspirin inhibits

Arachidonic Acid

Cyclo-oxygenase

PGE2PGF2

•Vasodilation•Maintain CL•Ovulation•Implantation

•Vasoconstriction•CL regression•Ovulation•Parturition•Sperm transport

Other Hormones

B. Melatonin1. Secreted from the pineal gland.

2. Is a modified amino acid

3. Functions to integrate effects of light on reproductive processes.

Other Hormones

C. Human Menopausal Gonadotropin (hMG)1.Anterior pituitary gland

» Secreted in menopause, FSH-like activity

» Isolated from urine

a. Perganol - superovulation

Classification and Properties of Hormone

A.Site of Production

B.Type of action

1. Primary hormone of reproduction (FSH, LH, estradiol, progesterone)

2. Metabolic hormone (thyroxin, insulin, STH)

Classification and Properties of Hormone

• Chemical Structure»Polypeptides - hypothalamic

»Protein - pituitary, gonad

»Steroids - gonad, adrenal

»Fatty acid - many sources, prostaglandins

»Modified amino acid - pineal

Chemical Structure of Hormones

polypeptide modified amino acid protein sex steroid fatty acid

GnRh melatonin LH Estradiol PGF

TRH FSH Progesterone

CRH Prolactin Testosterone

GHRH ACTH

Somatistatin TSH

Oxytocin GH or STH

Relaxin

Inhibin

2

Chemical Structure of HormonesMolecular size of hormones that regulate reproduction

Hormone Molecular

WeightFSH 30,000 to 37,000LH 26,000 to 32,000Prolactin 23,000 to 25,000HCG 37,700eCG 28,000Inhibin >10,000Relaxin 6,500ACTH 4,500Oxytocin 1,007GnRH 1,200Estradiol 300Testosterone 300Progesterone 300PGF 300

2

Chemical Structure of Hormones Cont.

Polypeptide and protein hormonesare made of peptide bonds

NH3

CH

C

HN

HC

C

NH

CH

COO-

R

O

R

O

R

PeptideBond

These hormones can not be given orally!These hormones can not be given orally!

Chemical Structure of Hormones Cont.

SteroidsCHOLESTEROL

PREGNENOLONE

CORTISOL

ADRENAL OVARY OR TESTES

PROGESTERONE

OH-PROGESTERONE

ANDROSTEINDIONE ESTRONE

TESTOSTERONE ESTRADIOL

17α

PROGESTERONE

CORTISOL

These hormones can be given orally!These hormones can be given orally!

Mechanism of Hormone Action

Mechanism of Hormone Action

Receptor Structure

Mechanism of Hormone Action

LH

RECEPTOR

ATP cyclic AMP

Protein Kinase

Nucleus

DNAhistones

phosphorylates

mRNA Protein Synthesis(Enzymes)

CholesterolPregnenolone

Testosterone

CELL MEMBRANE

phosphorylationof enzymes in

steroid synthesis

Protein synthesis thatregulates steroid synthesis

(enzymes)

Mitochondria

Protein Hormones(cAMP second messenger)

Protein Hormones(cAMP second messenger)

Adenylate cyclase

Cholesterol

G

cAMP Second Messenger Hormones

• Anterior Pituitary Hormones»LH, FSH, Prolactin

»STH, ACTH, TSH

• Placental Hormones»HCG, eCG

Protein Hormones (Ca2+ Second Messenger)Protein Hormones (Ca2+ Second Messenger)

GnRH

Receptor

Receptor

GnRH

Receptor

Receptor

G-proteinG-protein

PLC

Phosphotidyl Inositol

DAG

IP3

Endoplasmic Reticulum

R

Ca2+

Ca2+

PKC

LH

SecretoryGranules

Fusion

Plasma Membrane

Plasma Membrane

Ca2+

Calcium Second Messenger Hormones

• GnRH» triggers release of LH in anterior pituitary

• Oxytocin» triggers contractions of smooth muscle

• PGF2

» triggers apoptosis of cell

» inhibition of progesterone synthesis

Steroid Hormone Action

STEROID(estrogen)

Cytoplasm Diffusion?

Cell Membrane

DNA

Receptor

NucleusmRNA

Protein Synthesis

Change in CellPhysiology

UterineGrowth

Feedback Loops

Hypothalamus

Releasing Hormones

Neuro-secretory Cells

Portal Vein

Anterior Pituitary

Gonadotropins: FSH, LH

Blood Stream

GonadsReceptor on Cell Surface

Cyclic AMP inside cell

Steroid Hormone Production

Blood Stream

-

-

Polypeptides

Proteins

Why only effects on target organs[ ]

{TestosteroneEstradiolProgesterone

Bound to Protein