Download Endocrinology of reproduction I (Lecture 6 and 7 combined)

Animal Science 434
Reproductive Physiology
Lecture 6 and 7:
Endocrinology
What is the function of the
endocrine system?
Integration of Body Functions
• nervous and endocrine system are similar
• nervous system
»
seconds
»
minutes and hours
• endocrine system
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.
Endocrine Glands
Hypothalamus
Pineal
Adrenal
Ovary
Uterus
Pituitary
Placenta
Testes
(in bull)
Thyroid
Pancreas
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.
B.
•
•
Structure
short chain polypeptides (3 - 44 amino acids)
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
Hypothalamus
Preoptic
nuclei
cell
Nerve
Cells
Superior
hypophyseal
artery
Capillary plexus
Hypophyseal
portal vessels
Cells of the
Anterior
Pituitary
•
•
•
•
•
•
LH
FSH
Prolactin
STH
TSH
ACTH
Posterior
pituitary
Capillary
plexus
Anterior Pituitary Hormones
A. Structure
1. glycoproteins or proteins
B. Hormones
1. gonadotropins
» Follicle stimulating hormone
» Luteinizing hormone (LH)
» Prolactin
(FSH)
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

S
•
•
S
b
 chains
are the same
b chains differ and give specificity
Hypothalamus
Supraoptic
nuclei cell
Nerve
Cells
Paraventricular
nuclei cell
Capillary plexus
Anterior
Pituitary
Posterior
pituitary
• Oxytocin
• ADH
Hypothalamus
Nuclei that produce
posterior pituitary
hormones
Posterior Pituitary Hormones
A.Structure
• polypeptides (9 amino acids)
B.Hormone
•
Oxytocin - contraction of smooth muscle
Placental Hormones
A. Equine Chorionic Gonadotropin (eCG)
1.
2.
3.
4.
FSH-like activity (some LH)
long half-life
In blood and not urine
Function
– stimulates follicular growth during pregnancy
– LH-like activity stimulates follicles to form
accessory CLs
Placental Hormones (cont.)
5. Other commercial hormones from the equine
placenta
• Estrogens (several)
 Found in mare urine
 Premarin is commercial name
 Treatment of postmenopausal women
 Estrogen replacement therapy
 Prevents osteoporosis
 Reduces heart disease
Placental Hormones (cont.)
B. Human Chorionic Gonadotropin (HCG)
1. LH-like activity.
2. In blood and urine.
3. Function
–
prevents CL regression
C. Placental Lactogen (PL)
1. Has both GH- and prolactin-like activity.
2. Development of mammary gland
Gonadal Polypeptide Hormones
A. Relaxin
1. Secreted by CL during pregnancy.
2. Prior estrogen exposure required
3. Functions
– cervical dilation
– inhibits uterine contractions
Gonadal Polypeptide Hormones
B. Inhibin
1. Male - Sertoli cells
2. Female - granulosa cells
3. Function
–
inhibits FSH secretion without altering
LH secretion
Gonadal Steroids
A. General
1. Origin - ovary, testis, adrenal
2. Structure
Steroid
Cholesterol
27-C
Synthesis
Pregnenolone
21-C
OH
Estradiol
18-C
HO
19-C
21-C
Progesterone
Testosterone
Gonadal Steroids Cont.
B.Androgens
1. Testosterone.
2. Source
a)
b)
c)
Male - Leydig cells
Female - theca interna
Adrenal
3. Bound in blood
Gonadal Steroids cont.
4. Function in the male
– spermatogenesis
– epididymis
– accessory sex glands and secondary
– male secondary sex characteristics
– anabolic activity
– inhibits GnRH and LH release
sex organs
Gonadal Steroids Cont.
C. Estrogens
1. Estradiol.
2. Female - granulosa cells, placenta, adrenal
3. Male - Sertoli cells, adrenal
4. Transported in blood by steroid binding globulin
Gonadal Steroids Cont.
4.Functions
• CNS
• Uterus growth
• Uterus contraction
• female secondary sex characteristics
• mammary gland
• stimulates or inhibits GnRH and LH release
• nonreproductive
a. calcium uptake and bone ossification
b. anabolic and growth effects
Gonadal Steroids Cont.
D. Progestins
1. An example is progesterone
2. Produced in the CL, the placenta and the
adrenal gland.
3. Transported in the blood bound to steroid
binding globulin.
4. Functions
– prepares the uterus for implantation and pregnancy
– acts with estrogen to induce the behavior patterns of
estrus
– develops alveoli of mammary gland
– inhibits the rise of LH that causes ovulation by
inhibiting GnRH and LH release
Steroid
Cholesterol
Synthesis
Pregnenolone
Mitochondria
OH
Estradiol
HO
Smooth ER
Progesterone
Testosterone
Other Hormones
A. Prostaglandins
1. An example is PGF2
Lipid Hormones - Prostaglandins
Fatty Acids
Prostaglandins
Phospholipids
1. Produced by all tissues
- Rate limiting (Phospholipase A2)
of body
2. Can have a local effect
on tissues (same tissue
Arachidonic Acid - Precursor to Prostaglandins
which produced it)
Cyclo-oxygenase
3. Rapidly degraded in lungs
Aspirin inhibits
•Vasodilation
•Maintain CL
•Ovulation
•Implantation
PGE2
PGF2
•Vasoconstriction
•CL regression
•Ovulation
•Parturition
•Sperm transport
Other Hormones
B. Melatonin
1. 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
a. menopause.
2. FSH-like activity
a. long half-life.
b. no estradiol feedback.
3. In urine
a. Perganol
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
GnRh
melatonin
TRH
CRH
GHRH
Somatistatin
Oxytocin
protein
sex steroid
fatty acid
LH
Estradiol
PGF2
FSH
Progesterone
Prolactin Testosterone
ACTH
TSH
GH or STH
Relaxin
Inhibin
Chemical Structure of Hormones
Molecular size of hormones that regulate reproduction
Hormone
FSH
LH
Prolactin
HCG
eCG
Relaxin
ACTH
Inhibin
Oxytocin
GnRH
Estradiol
Testosterone
Progesterone
PGF
2
Molecular Weight
30,000 to 37,000
26,000 to 32,000
23,000 to 25,000
37,700
28,000
6,500
4,500
>10,000
1,007
1,200
300
300
300
300
Chemical Structure of Hormones Cont.
Polypeptide and protein hormones
are made of peptide bonds
NH 3
R
CH
C
O
HC
R
HN
O
Peptide
Bond
C
NH
R
CH
COO-
These hormones can not be given orally!
Chemical Structure of Hormones Cont.
Steroids
CHOLEST EROL
PREGNENOLONE
ADRENAL
OVARY OR T EST ES
CORTISOL
PROGESTERONE
PROGESTERONE
 OH-PROGEST ERONE
CORTISOL
ANDROST EINDIONE
T EST OST ERONE
ESTRONE
ESTRADIOL
These hormones can be given orally!
Mechanism of Hormone Action
Mechanism of Hormone Action
Protein Hormones
(cAMP second messenger)
LH
RECEPTOR
CELL MEMBRANE
Adenylate cyclase
ATP
cyclic AMP
Testosterone
phosphorylation
of enzymes in
steroid synthesis
Pregnenolone
Protein Kinase
Cholesterol
Mitochondria
phosphorylates
histones
DNA
Cholesterol
Protein synthesis that
Protein
regulates steroid synthesis
Synthesis
(enzymes)
(Enzymes)
mRNA
Nucleus
cAMP Second Messenger Hormones
•
Anterior Pituitary Hormones
•
Placental Hormones
» LH, FSH, Prolactin
» STH, ACTH, TSH
» HCG,
eCG
Protein Hormones (Ca2+ Second Messenger)
Ca
GnRH
Receptor
Receptor
GnRH
G-protein
Plasma
Membrane
Phosphotidyl
Inositol
DAG
PLC
IP3
Ca
R
Ca
PKC
2+
2+
Endoplasmic Reticulum
Secretory
Granules
Fusion
Plasma Membrane
LH
2+
Calcium Second Messenger Hormones
•
•
•
GnRH
» triggers
release of LH in anterior pituitary
Oxytocin
» triggers
PGF2
contractions of smooth muscle
» triggers apoptosis of cell
» inhibition of progesterone synthesis
Receptor
Structure
Steroid Hormone Action
STEROID
(estrogen)
Cell Membrane
Diffusion?
Cytoplasm
Uterine
Growth
Change
in Cell
Physiology
Receptor
DNA
mRNA
Protein
Synthesis
Nucleus
Hypothalamus
Feedback
Loops
Neuro-secretory Cells
Releasing Hormones
Polypeptides
Portal Vein
Anterior Pituitary
Gonadotropins: FSH, LH
Proteins
Blood Stream
Gonads
Receptor on Cell Surface
only effects on
[ Why
]
target organs
Cyclic AMP inside cell
Steroid Hormone Production
{
Testosterone
Estradiol
Progesterone
Blood Stream
Bound to Protein