Classification of Repro hormones Bovines. pptx

Classification of Reproductive Hormones and their Role
Endocrine system
Classification of hormones
Hormones of hypothalamus
Anterior Pituitary hormones
Posterior Pituitary hormones
Gonadal hormones
Placental hormones

Suggested reading:��Pathways to pregnancy and parturition. 2005. by P.L. Senger;
Chapter 5.pages 110-121
Chapter 5.pages 122-123
Chapter 5, 14: pages 112-114; 314-318.

1. Classification of Reproductive Hormones and their Role Dr. Aman Ullah Zubair [DVM][RVMP]

2. Matrix Endocrine system Classification of hormones Hormones of hypothalamus Anterior Pituitary hormones Posterior Pituitary hormones Gonadal hormones Placental hormones

3. Endocrine System Endocrine system consists of endocrine glands which release hormones 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)

4. Testes (in bull) Placenta Uterus Ovary Adrenal Pineal Hypothalamus Pituitary Pancreas Thyroid Endocrine Glands

5. Endocrine Gland A ductless gland Secretes substances (hormones) into blood or lymph that affect cells elsewhere in the body Action of the hormone depends upon its half life

6. Exocrine Gland A gland with ducts that are used for secretion Examples; Liver, Pancreas, Parotid

7. Hormone Substance produced by endocrine gland Acts on cells, tissues or organs at a place other than where produced

8. Patterns of hormone secretion GnRH LH T

9. Classification and Properties of Hormone Chemical Structure Polypeptides - hypothalamic Protein - pituitary, gonad Steroids - gonad, adrenal Fatty acid - many sources, prostaglandins Modified amino acid - pineal

10. Chemical Structure of Hormones Polypeptide Modified amino acid Protein S ex 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 

11. Chemical Structure of Hormones Molecular size of hormones that regulate reproduction Hormone Molecular Weight FSH 30,000 to 37,000 LH 26,000 to 32,000 Prolactin 23,000 to 25,000 HCG 37,700 eCG 28,000 Inhibin >10,000 Relaxin 6,500 ACTH 4,500 Oxytocin 1,007 GnRH 1,200 Estradiol 300 Testosterone 300 Progesterone 300 PGF 300 2 

12. Releasing Hormones of the Hypothalamus 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) GH release Somatostatin (growth hormone inhibiting hormone) Inhibits GH Prolactin inhibiting hormone (Dopamine) Inhibits PRL

13. Hypothalamus Nuclei that produce posterior pituitary hormones SNS ↑ Conserves heat PNS ↑

14. Gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH), is a peptide chain of 10 amino acids. It stimulates the synthesis and release of the two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) It is secreted in pulsatile manner. In normal individuals, GnRH is released in spurts at intervals of about 80 minutes.

15. Clinical Uses of GnRH True anoestrus Improvement of conception rate (at the time of AI) Ovarian cyst (Follicular), irregular oestrus, Nymphomania Delayed Ovulation and Anovulation Improvement of pregnancy rate (11-12 day post AI) Improvement of post partum fertility (10-15 days post-calving)

16. Gonadotropin Releasing Hormone Conceptal (Star): Each ml contains Buserelin Acetate (MS) 0.0042 mg equivalent to 0.004 mg Buserelin (BP) Dose for cattle: 2.5-5ml i/m Dalmarelin (Fatro): 1 ml contains Active substance: Lecirelin acetate equivalent to lecirelin 25ug/ml Dose in cows: 2ml (50 ug) Cystorelin  (Merial): Inj. Gonodorelin - 50 µg / ml Natural GnRH) - 2ml, 10 ml vial. Dose in cow: 2ml (100ug) i/m Fertagyl  (Intervet): Inj. Gonadorelin 43 µg/ml (Natural GnRH). 5ml vial. Dose for cow: 2ml (86ug) i/m

17. Pituitary Gland The pituitary gland is pea-sized structure located at the base of the brain. It consists of two lobes: the Anterior Lobe and the Posterior Lobe The Anterior Lobe The anterior lobe contains five types of secretory cells All of them secrete their hormone in response to hormones reaching them from the hypothalamus of the brain.

18. Luteinizing Hormone (LH) LH is synthesized within the same pituitary cells as FSH and under the same stimulus (GnRH). It is also a heterodimeric glycoprotein consisting of The same 89-amino acid alpha subunit found in FSH and TSH (as well as in chorionic gonadotropin ); A beta chain of 121 amino acids that is responsible for its properties.

19. Luteinizing Hormone (LH) The effects of LH also depend on sex. LH in females In sexually-mature females, LH acts on theca interna cells of ovarian follicles to produce androgens which cross the basal membrane and enters granulosa cells. These granulosa cells produce estrogen under the action of FSH. A surge of LH triggers the completion of meiosis I of the egg and its release (ovulation) Stimulates the now-empty follicle to develop into the corpus luteum, which secretes progesterone

20. Luteinizing Hormone (LH) LH in males LH acts on the interstitial cells (also known as Leydig cells) of the testes stimulating them to synthesize and secrete the male sex hormone, testosterone . LH in males is also known as interstitial cell stimulating hormone (ICSH).

21. Follicle-Stimulating Hormone (FSH) FSH is a heterodimeric glycoprotein consisting of the same alpha chain found in TSH (and LH) a beta chain of 118 amino acids, which gives it its unique properties. Synthesis and release of FSH is triggered by the arrival from the hypothalamus of gonadotropin-releasing hormone (GnRH). The effect of FSH depends on one's sex

22. Follicle-Stimulating Hormone (FSH) FSH in females In sexually-mature females, FSH (assisted by LH) acts on the follicle s to mature and stimulate them to release estrogens . FSH in males In sexually-mature males, FSH acts on Sertoli cells for sperm maturation.

23. Antrum Theca Externa Theca Interna Granulosa Cumulus Oophorus Oocyte (Follicular Fluid) Tertiary Follicle Basement Membrane LH Receptors FSH Receptors

24. Prolactin (PRL) Prolactin is a protein of 198 amino acids and consist of single polypeptide chain rather than two subunits. Prolactin promotes the synthesis of milk. Prolactin secretion is stimulated by TRH Repressed by estrogens and dopamine .

25. The Posterior Lobe The posterior lobe of the pituitary releases two hormones, both synthesized in the hypothalamus, into the circulation. Antidiuretic Hormone (ADH). ADH is a peptide of 9 amino acids. It is also known as arginine vasopressin. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood. This acts to reduce the volume of urine formed (giving it the name of antidiuretic hormone).

26. Oxytocin Oxytocin is a peptide of 9 amino acids It acts on certain smooth muscles: stimulating contractions of the uterus at the time of birth (action on myometrial smooth muscles); stimulating release of milk when the newborn begins to suckle (action on myoepithelium around alveoli). Oxytocin is often given to prospective mothers to hasten birth in human and equine.

27. Gonadal Hormones Ovaries Steroid; Estrogen, Progestin Protein; Relaxin, Inhibin, Activin, Follistatin Testes Steroids; Androgen, Estrogen Protein; Inhibin

28. Gonadal Steroids 21-carbon steroid → has progestogen properties 19-carbon steroid → has androgen activity 18-carbon steroid → has estrogen activity In blood plasma, steroid hormones are mostly bound to albumin

29. Steroids are organic compounds that contain four rings of carbon atoms Cyclopantanoperhydrophenanthrene

30. Progestogens (C-21) Source: Corpus luteum Functions Non pregnant animal Negative feed back on GnRH and thus decreases LH, FSH Inhibits estrus and the ovulatory surge of LH Acts synergistically with estrogens to induce behavioral estrus Pregnant animal Negative feed back on GnRH and thus decreases LH, FSH Prepares the endometrium for implantation and maintenance of pregnancy Inhibits uterine motility Develops the secretory tissue (alveoli) of the mammary glands

31. Progesterone (Chemistry) Progesterone is   pregnane  (C21)  steroid  and is also known as pregn-4-ene-3,20-dione. It has a  double bond  ( 4-ene ) between the C4 and C5 positions (thus called P4) and two  ketone   groups  (3,20- dione ), one at the C3 position and the other at the C20 position.

32. Progestogens (C-21) Clinical Use Synchronization of estrus Feeding, injection, sponges, implants, CIDR Prolapse of pregnant uterus Threatened abortion

33. Androgens (C-19) Testosterone is an androgen produced by the interstitial cells (leydig cells) of the testes Functions Stimulate late stages of spermatogenesis and prolong the life span of epididymal sperm Maintain secondary sex characteristics and sexual behavior or libido of the male Clinical Use Teasers HRT (Human)

34. Estrogens (C-18) Source: ovarian follicle Granulosa cells Functions Acts on CNS to induce behavioral estrus in female Increase uterine contractions Development of female secondary sexual characteristics Negative and positive feedback controls on LH and FSH release through the hypothalamus The negative effect is on the tonic centre in the hypothalamus, and the positive effect is on the preovulatory (surge) centre Stimulate duct growth and cause the development of the mammary glands

35. Estrogens (C-18) Clinical Uses In ruminants, estrogens have a protein anabolic effect to increase body weight gain and growth Diethylstilbestrol (DES), synthetic nonsteroidal estrogen, was formerly used for growth promotion in cattle and sheep Induction of heat in cows

36. Cholesterol to Estrogens (Two cell theory)

37. Relaxin Nature: Polypeptide consisting of alpha and beta subunits connected by two disulfide bonds Molecular wt 5700 daltons Source: Corpus luteum during pregnancy Functions Relaxin dilates the cervix and vagina before parturition. Inhibits uterine contractions and causes increased growth of the mammary gland if given in conjunction with estradiol

38. Inhibin Nature Protein comprising two disulfide bridged subunits called α and β Molecular wt >10,000 daltons Source: Sertoli cells in male Granulosa cells in female Functions Inhibin reduce the secretion of FSH to a level, which maintains the species specific number of ovulation in both single and litter bearing species Regulate Leydig cell function

39. Activins Nature Protein Molecular weight 34000 daltons Found in follicular fluid, stimulates the secretion of FSH

40. Follistatin Nature Protein Molecular weight 35000 daltons Isolated from follicular fluid Follistatin not only inhibits the secretion of FSH similar to that of inhibins but also binds activin and neutralizes its biological activity Thus it modulates the secretion of FSH

41. Pacental Hormones Equine chorionic gonadotropin (eCG) Human Chorionic gonadotropin (hCG) Placental lactogen (PL) Protein B (IF τ ) Progesterone Estrogen Relaxin Prostaglandin F2 α Prostaglandin E2

42. Equine Chorionic Gonadotropin (eCG) The endometrial cups in pregnant mare are the source for the eCG The cups that are formed at about day 40 of pregnancy persist until day 85 of pregnancy eCG is a glycoprotein with α and β subunits similar to LH and FSH but with a higher carbohydrate content, especially sialic acid β sub unit has 149 amino acids

43. eCG production is related to weight of endometrial cups

44. Luteal P4 in 1 st half of pregnancy in mare

45. Equine Chorionic gonadotropin Functions eCG has both FSH and LH biological actions, with FSH actions being dominant. eCG circulates in the blood of pregnant mares and is not excreted in urine. The secretion of eCG stimulates development of ovarian follicles The follicles ovulate and form accessory corpora lutea (CLs). These CLs produce P4 which maintain pregnancy in the mare

46. eCG Clinical Use Superovulation (3000 i.u) Anoestrus (500-1000 i.u)

47. Human Chorionic Gonadotropin (hCG) Synthesized by trophoblastic cells in the primate placenta It is detected in the urine 6 days after conception Found both in blood and urine Glycoprotein, α and β subunits α subunit has 92 amino acids and two carbohydrate chains. The α subunit of hCG is similar to the α subunit of human, porcine and bovine LH. The β subunit has 145 amino acids and five carbohydrate chains.

48. Syncytiotrophoblast

49. hCG   Alpha 92 aa Beta 145 aa Held by ionic & hydrophobic forces (Lapthorn et al. Nature, 1994: 455-461)

50. Human Chorionic Gonadotropin Functions hCG is primarily luteinizing and luteotropic and has little FSH activity Clinical Uses To cause ovulation (1500-3000 i.u) Repeat breeding Increase conception Basis for human pregnancy tests

51. Placental Lactogen Placental lactogen is a protein with chemical properties similar to prolactin and growth hormone. It is found in rat, mice, sheep, cow & human Functions It is important in regulating maternal nutrients to the fetus and is important for fetal growth Placental lactogen may play a role in milk production because the level is higher in dairy cows (high milk producers) than in beef cows

52. Placental lactogen in blood near the end of gestation

53. Progesterone (P4) P4 is necessary for early embryonic development It provides stimulus for elevated secretions by endometrial glands High P4 is important for P4 block that inhibits myometrial contractions In ewe, mare & woman the CL is not needed for entire gestation because placenta takes over production of P4

54. Progesterone during gestation

55. Relaxin Placental relaxin is produced in human, mares, cats, dogs, rabbits & monkeys Relaxin is not present in bovine placenta at any stage of pregnancy Maternal blood relaxin forms basis for pregnancy test in bitch around day 30

56. Uterine Hormones PGF2 α : Secreted from walls of uterus in pulsatile manner Functions Regression of CL Stimulate myometrial contractions Ovulation Sperm transport • Vasoconstriction • Parturition

57. Uterine Hormones PGE2 Functions Uterine contractions • Vasodilatation • Maintain CL • Ovulation • Implantation

58. COOH o o COOH OOH o o COOH OH O OH COOH OH COOH OH OH OH Prostaglandins Many tissues Local effects Degraded in lung Phospholipids PLA 2 Cyclo-oxygenase Inhibited by aspirin PGE 2 PGF 2 PGH 2 PGG 2 Arachidonic Acid

59. COOH o o COOH OOH o o COOH OH O OH COOH OH COOH OH OH OH Phospholipids PLA 2 Cyclo-oxygenase Vasodilation Maintain CL Ovulation Implantation Vasoconstriction CL regression Ovulation Parturition Sperm transport PGE 2 PGF 2 PGH 2 PGG 2 Arachidonic Acid

60. CL Regression by PGF2 α

61. Pathways to pregnancy and parturition. 2005. by P.L. Senger; Chapter 5.pages 110-121 Chapter 5.pages 122-123 Chapter 5, 14: pages 112-114; 314-318. Suggested reading:

62. Thank You