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 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 (PGF 2  ) » 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 Ovary Adrenal Pineal 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 ( 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 Hypothalamus Nerve Cells Superior hypophyseal artery Hypophyseal portal vessels Capillary plexus Posterior pituitary Capillary plexus Preoptic nuclei cell

Anterior Pituitary Hormones A.Structure 1.glycoproteins or proteins B.Hormones 1.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   SS

Hypothalamus Nerve Cells Posterior pituitary Oxytocin ADH Paraventricular nuclei cell Supraoptic nuclei cell Anterior Pituitary Capillary plexus

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.FSH-like activity (some LH) 2.long half-life 3.In blood and not urine 4.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 Synthesis OH HO Cholesterol Pregnenolone Estradiol Progesterone Testosterone 27-C 21-C 19-C 18-C 21-C

Gonadal Steroids Cont. B.Androgens 1.Testosterone. 2. Source a) Male - Leydig cells b) Female - theca interna c) Adrenal 3. Bound in blood

Gonadal Steroids cont. 4.Function in the male – spermatogenesis – epididymis – accessory sex glands and secondary sex organs – male secondary sex characteristics – anabolic activity – inhibits GnRH and LH release

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 Synthesis OH HO Cholesterol Pregnenolone Estradiol Progesterone Testosterone Mitochondria Smooth ER

Other Hormones A.Prostaglandins 1.An example is PGF 2 

Lipid Hormones - Prostaglandins Fatty Acids Prostaglandins 1. Produced by all tissues of body 2. Can have a local effect on tissues (same tissue which produced it) 3. Rapidly degraded in lungs Phospholipids - Rate limiting (Phospholipase A 2 ) - Precursor to Prostaglandins Aspirin inhibits Arachidonic Acid Cyclo-oxygenase PGE 2 PGF 2  Vasodilation Maintain CL Ovulation Implantation 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 polypeptidemodified amino acidproteinsex steroidfatty acid GnRhmelatoninLH EstradiolPGF TRHFSH Progesterone CRHProlactinTestosterone GHRHACTH SomatistatinTSH OxytocinGH or STH Relaxin Inhibin 22

Chemical Structure of Hormones Molecular size of hormones that regulate reproduction HormoneMolecular Weight FSH30,000 to 37,000 LH26,000 to 32,000 Prolactin23,000 to 25,000 HCG37,700 eCG28,000 Relaxin6,500 ACTH4,500 Inhibin>10,000 Oxytocin1,007 GnRH1,200 Estradiol300 Testosterone300 Progesterone300 PGF300 22

Chemical Structure of Hormones Cont. Polypeptide and protein hormones are made of peptide bonds These hormones can not be given orally!

Chemical Structure of Hormones Cont. Steroids PROGESTERONE CORTISOL These hormones can be given orally!

Mechanism of Hormone Action

phosphorylation of enzymes in steroid synthesis Protein synthesis that regulates steroid synthesis (enzymes) Mitochondria Protein Hormones (cAMP second messenger) Protein Hormones (cAMP second messenger) Adenylate cyclase Cholesterol

cAMP Second Messenger Hormones Anterior Pituitary Hormones » LH, FSH, Prolactin » STH, ACTH, TSH Placental Hormones » HCG, eCG

Protein Hormones (Ca 2+ Second Messenger) GnRHReceptor Receptor G-protein PLC Phosphotidyl Inositol DAG IP 3 Endoplasmic Reticulum R Ca 2+ Ca 2+ PKC LH Secretory Granules Fusion Plasma Membrane Plasma Membrane Ca 2+

Calcium Second Messenger Hormones GnRH » triggers release of LH in anterior pituitary Oxytocin » triggers contractions of smooth muscle PGF 2  » triggers apoptosis of cell » inhibition of progesterone synthesis

Receptor Structure

Steroid Hormone Action Uterine Growth

Feedback Loops Hypothalamus Releasing Hormones Neuro-secretory Cells Portal Vein Anterior Pituitary Gonadotropins: FSH, LH Blood Stream Gonads Receptor on Cell Surface Cyclic AMP inside cell Steroid Hormone Production Blood Stream - - Polypeptides Proteins Why only effects on target organs [ ] { Testosterone Estradiol Progesterone Bound to Protein