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Chapter 4 Natural Synchronization Processes

Chapter 4 Natural Synchronization Processes. Dr. Hatem Atalla. Major endocrine systems for regulation of reproductive processes:. Brain Diagram of Endocrine Glands. Types of glands. 1) Endocrine glands: Don't have ducts. Secrete hormones internally into blood stream.

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Chapter 4 Natural Synchronization Processes

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  1. Chapter 4 Natural Synchronization Processes Dr. Hatem Atalla

  2. Major endocrine systems for regulation of reproductive processes:

  3. Brain Diagram of Endocrine Glands

  4. Types of glands • 1) Endocrine glands:Don't have ducts. Secrete hormones internally into blood stream. • 2) Exocrine glands:Have ducts. Secrete externally into ducts. • Definition of Hormones:Chemical agents which are carried by the blood to cells within a target organ or other target cells where they regulate a specific physiological activity. • Definition of Receptor sites: 1) Recognition units in cells that have a high affinity for a particular hormone 2) Chemically: Protein 3) Hormone + receptor site: initiates reactions within cell which bring about the specific physiological response within that bound hormone. 4) Location of receptor sites in a cell:     Cytosol receptor: For steroid hormones Membrane receptor: For peptide or protein hormones 5) Concentration of receptor sites in a target organ:    increase or decrease depending on the endocrine status of the animal.

  5. Hormone • Hormone - Chemical messenger produced by a ductless gland or tissue and carried in the blood to a target organ where it effects a change in cellular activity. • Functionally; reproductive hormones are classified into: • Primary hormones: regulate the various reproductive processes • Metabolic hormones: which indirectly influence reproduction.

  6. Classification According to their Chemical Structure • Proteins:*Are Polypeptide hormones, *M.W=300-70,000 Daltons.*Because they are easily digested by enzymes, they cannot be given orally, but must be administrated by injection. • Steroids:*M.W.=300-400 Daltons.*Natural steroids are not effective by oral administration, but synthetic or plant steroids can be administrated orally and by injection. • Fatty Acids:*M.W.= 400 Daltons*Can be administrated only by injection.

  7. Classification According to their Chemical Structure

  8. Table 4-2. Hormones that Regulate Reproduction: Hypothalamus

  9. Table 4-2. Hormones that Regulate Reproduction: Anterior Pituitary

  10. Table 4-2. Hormones that Regulate Reproduction: Ovary

  11. Table 4-2. Hormones that Regulate Reproduction: Testis & Adrenal Cortex

  12. Table 4-2. Hormones that Regulate Reproduction: Placenta & Uterus

  13. 4-1 Primary reproductive hormones of pituitary gland • Pituitary (Hypophysis, Hypophyseal gland): in bony depression at base brain • Embryologically and functionally two separate glands Anterior pituitary (adenohypophysis) embryonic gut of mouth roof GTH: FSH and LH in domestic animals (LH=ICSH: Interstitial cell stimulating hormone in male) prolactin (PRL): LTH (luteotropic hormone) in rodents • Posterior ptituitary (neurohypophysis) embryonic brain, neuroendocrine gl. Oxytocin

  14. FSH: • 1) Stimulate follicle growth 2) Stimulate estrogen production by granulosa cells in ovarian follicle 3) Inhibin secretion by granulosa cells with its production being enhanced by FSH and testosterone • Inhibin: 1) inhibit FSH secretion 2) Found In testes, but richer in follicular fluid 3) In males: inhibit spermiogenesis 4) FSH stimulate Sertoli cells: to release inhibin and androgen binding porotein( ABP) ABP = a carrier for T • LH: • 1)cause Testosterone release from theca interna cells--- converted to estrogens by granulosa cells by FSH 2) causes maturation of oocytes and ovulation 3) luteotropic = formation of CL (corpus luteum) & production of P4 (progesterone) 4) In males: causes the Leydig cells in interstitial tissue to release testosterone and other androgens • PRL: • 1) synergizes with LH: by increasing LH receptor sites in CL in some species to release P4 2)causes development of mammary gland and synthesis of milk 3) In males: synergizes with LH: by increasing LH receptor sites in Leydig cells to secret Testosterone. • ACTH: • Causes release of glucocorticoids from adrenal cortex Gluococorticoids: causes parturition and synthesis of milk

  15. In males: • FSH stimulates spermiogenesis in the testes with action on both spermatogonia and Sertoli cells. • FSH stimulates the Sertoli cells to produce inhibin and androgen binding protein (ABP). • Since inhibin has not been fully characterized, it is frequently referred to as either testicular inhibin or ovarian inhibin, depending on its source. ABP is secreted into the lumen of the seminiferous tubules and serves as a carrier for testosterone. • LH stumulates Leydig cells to release Testosterone. • Prolactin appears to synergize with LH by increasing hormone receptor sites LH in the testes. • Oxytocin, a peptide hormone released from posterior pituitary, stimulates the contraction of smooth muscle in the oviduct and uterus. Because of this activity, it has been postulated that oxytocin aids both sperm and ovum transport in the female tract and stimulates uterine contractions during parturition. Also, oxytocin stimulates the myoepithelial cells of the mammary gland, causing the ejection of milk.

  16. 4-2 Control of the pituitery Gland by the Hypothalamus • The hypothalamus is a neuroendocrine gland which forms along the floor and lateral wall of the third ventricle of the brain. • It is closely linked with the pituitary. The hypophyseal portal blood system connects the hypothalamus with anterior pituitary and is the route by which hormones of the hypothalamus reach the anterior pituitary. • The hypothalamic hormones are released from terminals of axons (nerve fibers) into blood vessels which serve the anterior pituitary • The area of the hypothalamus where this which receive releasing factors are median eminence and the pituitary vessels which receive releasing factors the hypophyseal portal vessels. • Also, a portion of the venous return from the anterior pituitary is by way of the hypothalamus. This permits a direct, short-loop feedback system whereby hormones of the anterior pituitary may help regulate release of hormones from the hypothalamus. • The posterior pituitary is an extension of the hypothalamus. Axons from neurosecretory cells in the hypothalamus extends down into the posterior of pituitary (Figure 4-3).

  17. Figure 4-3 Relationship between the hypothalamus and the pituitary gland 

  18. 4-2 Control of the pituitery Gland by the Hypothalamus • Secretion of gonadotropic hormones from the anterior pituitary is controlled by a peptide-releasing hormone which is produced by neurosecretory cells in the hypothalamus. • GnRH causes the release of both FSH and LH. At one time, it was postulated that separate releasing agents (FSH-releasing hormone and LH-releasing hormone) regulated the release of FSH and LH from the anterior pituitary. While some physiological evidence for separate releasing hormones still exists, the preponderance of evidence supports a single releasing hormone for FSH and LH. • In a clinical situation, GnRH can be used instead of LH for treatment of cystic ovaries in cows.

  19. 4-2 Control of the pituitery Gland by the Hypothalamus • There is evidence that both a prolactin releasing factor (PRF) and prolactin inhibiting factor (PIF) control the release and retention of prolactin in the anterior pituitary. • Corticotropin releasing hormone (CRH) stimulates the release of ACTH. • Oxytocin, which is released from the posterior pituitary, is produced by the supraoptic and paraventricular nuclei (neurosecretory cells) in the hypothalamus. After syntheses, oxytocin is transported by carrier proteins (neurophysins) as secretory droplets along nerve fibers extending into the posterior pituitary. Stimulation of sensory nerves in the teats or cervix will cause oxytocin to be released from nerve endings in the posterior pituitary.

  20. Hypothalamus Hypophysis Interrelation

  21. Anterior Pituitary

  22. Posterior pituitary

  23. Oxytocin Release

  24. 4-3 Hormones of the Gonads4-3.1 Female • Two classes of hormones produced by the ovaries are estrogens and progestins. Chemically, estrogens and progestins are classified as steroids and have cholesterol as a common precursor. • Estrogens, • representing a group of steroids with similar physiological activity, are produced by specified cells in the Graafian follicle. • The thecal cells of the follicle are stimulated by LH to produce testosterone which diffuses across the basement membrane, where it is converted to estrogens by granulosa cells under the influence of FSH. • The estrogen of greatest importance, quantitatively and physiologically, is estradiol. Others of importance include estriol and estrone. • The principal actions of estrogens are their influence on • (1) the manifestation of mating behavior during estrus; • (2) cyclic changes in the female tract; • (3) duct development in the mammary gland; and • (4) development of secondary sex characteristics in females. • Estrogens have been called the "female sex hormone.“ • Estrogens are luteolytic in cows and ewes but are luteotropic in sows.

  25. 4-3 Hormones of the Gonads4-3.1 Female • Progestins: • Are another group of hormones with similar physiological activity, the most important being progesterone. • They are produced by the granulosa cells in the corpus luteum under the influence of LH. • Important functions are • (1) inhibition of sexual behavior; • (2) maintenance of pregnancy by inhibiting uterine contractions and promoting glandular development in the endometrium; and • (3) promotion of alveolar development of the mammary gland. • The synergistic actions of estrogens and progestins are notable in preparing the uterus for pregnancy and the mammary gland for lactation.

  26. Clinical Applications of Estrogens • Plant Estrogens (isoflavons) are found primarily in legumes such as subterranean clover and alfalfa. Two of these compounds, Genistein and Coumestrol, cause infertility problems primarily in females and less frequently in males. • Zeronal (Ralgro), a compound with estrogen activity produced by a mold, is an ear implant and promotes growth of feedlot animals. • Estrogens have been used to abort cows and sheep because they have a luteolytic action (regression of CL), probably caused by PGF2ά.

  27. Clinical Applications of Progesterone • Progestogens are given to prevent abortion in females prone to abortion as a result of insufficient secretion of endogenous progesterone. • Synthetic progestogens are commercially available to synchronize the estrus cycle of cows.

  28. 4-3 Hormones of the Gonads4-3.1 Female • Both estrogens and progestins help regulate the release of gonadotropins, acting through both the hypothalamus and anterior pituitary (Figure 4-4). • High levels of either progestins or a combination of progestins and estrogens (second half of pregnancy) inhibit the release of GnRH, FSH, and LH from the anterior pituitary-a negative feedback control. • Near the time of estrus, when progesterone levels are low, high estrogen concentrations action on the hypothalamus stimulate the release of GnRH, LH, FSH, and prolactin - a positive feedback control. • The influence of the gonadotropins on estrogen and progestin release has been mentioned previously. Therefore, it can be seen that reciprocal (common) action between the gonadotropins and the steroid hormones of the ovaries is necessary for maintenance of the hormone balance essential for normal reproduction.

  29. Figure 4-4 Relationship between the hypothalamic releasing hormones, gonadotropins, and ovarian hormones in regulating reproductive function a. GnRH from the hypothalamus stimulates the release of FSH and LH from the anterior pituitary.b. FSH stimulates production of estradiol and inhibin by granulosa cells in the ovarian follicle.c. Inhibin selectively inhibits release of FSHd. When progesterone is low, high concentrations of estradiol stimulate a greater surge of GnRH, FSH, and LH, a positive feedback control. e. LH stimulates production and release of progesterone by granulisa cells in the corpus luteumf. High concentrations of progesterone inhibit the release of GnRH, FSH, and LH, a negative feedback control. 

  30. Female Feedback Diagram

  31. 4-3 Hormones of the Gonads4-3.1 Female • Inhibin, • a protein hormone produced by granulosa cells in the ovarian follicle, selectively suppresses release of FSH, but not LH, from the anterior pituitary. • The action of inhibin may account for some of the reported differences in the release patterns of FSH an LH that appear inconsistent with a single gonadotropin releasing hormone. • Relaxin • Is a polypeptide hormone produced by the corpus luteum and placenta. • Little is known about the mechanisms controlling its production, but higher concentrations are seen during pregnancy. • It causes a relaxation of pelvic ligaments and softening of the connective tissue of the uterine muscles to allow the expansion necessary to accommodate the growing fetus. • Synergizing with estrogen, it causes further expansion of the pelvis and softening of the connective tissue of the cervix to permit the fetus to be expelled during parturition.

  32. 4-3 Hormones of the Gonads4-3.1a Follicular fluid • Follicular fluid (liquor folliculi) is the fluid that fills the antrum of a tertiary follicle bathing the granulosa cells. • There is free exchange of fluids and many compounds between blood and follicular fluid across the basement membrane. However, large plasma proteins (>1,000,000 MW) do not cross the basement membrane and are not in follicular fluid. • Follicular fluid is rich in steroid reproductive hormones including testosterone, estradiol, and progesterone. • Concentrations of these steroids are much higher in follicular fluid than in blood. This is not surprising, since testosterone produced by theca cells is converted to estradiol in granulosa cells. • As the follicle matures, the increasing number of granulosa cells is reflected by the decreased concentration of testosterone while estradiol concentration increases.

  33. 4-3 Hormones of the Gonads4-3.1a Follicular fluid • The pituitary hormones, FSH, LH, and prolactin, are found in follicular fluid. • The lower concentrations of LH as compared to FSH may in part be due to binding of LH to theca cells outside the basement membrane, whereas granulosa cells have receptor sites for both FSH and LH. • FSH is needed for the conversion of testosterone to estradiol by granulosa cells, whereas LH stimulates progesterone production by granulosa cells. • Prolactin inhibits progesterone synthesis by granulosa cells (in vitro), and higher progesterone is seen in follicular fluid when prolactin is low. • Prostaglandins are found in the follicular fluid of Graafian follicles as the time of ovulation approaches (Section 4-6)

  34. 4-3 Hormones of the Gonads4-3.1a Follicular fluid • A number of other peptide ovarian factors have been identified in follicular fluid in recent years. • Of these, inhibin has been characterized most completely and has been mentioned previously (Sections 4-1 and 4-3.1). • It is a protein with various estimates on its molecular weight ranging from greater than 10,000 to greater than 70,000. • Its production by granulosa cells is enhanced by both FSH and testosterone. • Similarly, both FSH and testosterone have been reported to stimulate production of inhibin by Sertoli cells in the testes. • Inhibin selectively inhibits production of FSH while not affecting LH in both females and males. • Inhibin may serve to prevent overstimulation of the ovaries by FSH and may also be a factor in atresia (degeneration) of follicles that start development but do not ovulate during a given estrous cycle. • Because its site of action is the anterior pituitary, a site away from the organ where it is produced, inhibin can be classified as a hormone.

  35. 4-3 Hormones of the Gonads4-3.1a Follicular fluid • GnRH or a similar substance has been identified in follicular fluid. • The concentrations in follicular fluid are thought to be too high for it to be of hypothalamic origin, but cells in the ovary that secrete GnRH have not been identified. • GnRH will suppress production of estradiol and progesterone, thus interfering with ovulation and corpus luteum formation. • The concentration of GnRH that originates from the hypothalamus is not high enough in peripheral blood to have these depressing effects on ovarian function.

  36. 4-3 Hormones of the Gonads4-3.1a Follicular fluid • Oocyte maturation inhibitor, a factor which prevents resumption of meiosis until a few hours before ovulation, may be produced by granulosa cells under the influence of FSH. • A peptide with a molecular Wight of less than 10,000, its activity declines shortly before ovulation, thereby permitting meiosis to resume. • Other peptide factors with either stimulating or inhibiting effects on ovarian function are poorly characterized, but some will likely prove to be important to natural regulation of ovarian function. • Factors that have been reported in research literature include • luteinizing stimulator, • luteinizing inhibitor, • FSH receptor binding inhibitor, • gonadostatin and gonadocrinin, the latter having actions similar to GnRH.

  37. 4-3 Hormones of the Gonads4-3.2 Male • Upon stimulation by LH, the Leydig cells of the testes produce androgens, which are a class of steroid hormones. • The principal androgen in mature males is testosterone, which has been labeled the male sex hormone. • Dihydrotestosterone is found in high enough concentration in peripheral tissue to be of functional importance. • Functions of testosterone include • (1) development of secondary sex characteristics; • (2) maintenance of the male duct system; • (3) expression of male sexual behavior (libido); • (4) function of the accessory glands; • (5) function of the tunica dartos muscle in the scrotum; and • (6) spermatocytogenesis.

  38. 4-3 Hormones of the Gonads4-3.2 Male • The role of testosterone in regulating the release of hypothalamic and gonadotropic hormones is similar to that described for progesterone in the female (Figure 4-5). • High concentrations of testosterone inhibit the release of GnRH, FSH, and LH, a negative feedback control. • Conversely, when testosterone concentrations are low, higher levels of GnRH, FSH, and LH are released. • Thus, reciprocal action of testosterone with the hypothalamic and gonadotropic hormones is necessary for regulation of normal reproduction in the male. • Inhibin and androgenbinding protein are produced by Sertoli cells under the influence of FSH. • As in the female, inhibin selectively inhibits the release of FSH while not affecting the release of LH. Androgen binding protein binds testosterone, making it available for its functions in spermatozoa production. • Under the influence of FSH, Sertoli cells convert testosterone to estradiol, but a role for estradiol in regulation of reproduction in the male has not been clearly established.

  39. Figure 4-6 Interrelationship of the hormones regulating reproduction in the male.

  40. Male Feedback Diagram

  41. 4-4 Primary Reproductive Hormones of the Adrenal Cortex • The adrenal cortex produces two classes of steroid hormones which have been associated with mineral metabolism (mineralocorticoid) and carbohydrate metabolism (glucocorticoids). • Glucocorticoids, the principal one being cortisol, have been classified as anti-stress hormones, also. While progestins, estrogens, and androgens have been isolated from the adrenal cortex, they have not been seen in quantities high enough to affect the reproductive processes. • A role for glucocortidoids in the initiation of parturition in sheep has been demonstrated. • Furthermore, the glucocorticoids involved in this process are of fetal rather than maternal origin. This phenomenon has not been as clearly demonstrated in other classes of farm animals, but the evidence appears sufficiently strong to include glucocorticoids as a primary hormone of reproduction. • In addtion, a role for glucocorticoids in milk synthesis has been advanced (Chapter 10).

  42. 4-5 Endocrine Function of the Uterine/Placental Unit • The placenta does not fit the classical definition of an endocrine gland but does assume an endocrine function during pregnancy. • Estrogens, progestins, and relaxin are produced by the placenta in certain species and supplement production of these hormones by the ovaries. • In addition, placental hormone (s) with luteotropic and/or lactogenic activity have been identified in some species and may be present in others. • Human chorionic gonadotropin (HCG) has been isolated from the urine of pregnant women. Its principal action is LH-like and is believed to help maintain the function of the corpus luteum during pregnancy. • Pregnant mare serum gonadotropin (PMSG) is produced by endometrial cups which form when specialized cells in the chorion invade the endomitrium of the pregnant uterus of the mare. • Principally, PMSG has FSH-like action but it has some LH-like activity, also. It has been isolated from the serum of mares during early pregnancy. Both HCG and PMSG are proteins.

  43. 4-5 Endocrine Function of the Uterine/Placental Unit • Placental lactogen has been isolated from a number of species including goats, sheep, and cows. • It is a polypeptide and is extracted from the placenta of these species. • Its properties are similar to both proalctin and growth hormone. • Possible functions include • development of the mammary gland for postpartum milk production, • regulation of fetal growth through altered maternal or fetal metabolism, • and stimulation of progesterone synthesis by the ovary or fetal metabolism, • and stimulation of progesterone synthesis by the ovary or placenta. • Higher concentrations are seen during late gestation than early gestation. Higher concentrations have also been reported for cows with high milk production than for low milk producers.

  44. Placental Hormones and their Biological Action

  45. Pregnant Mare Serum Gonadotropin PMSG • This placental gonadotropin is secreted by the equine uterus. • The endometrial cups are formed at about day 40 of pregnancy and persist until day 150 of pregnancy. • The secretion of PMSG stimulates development of ovarian follicles. Some of these follicles ovulate, but most form a luteinized follicle, which is due to the LH-like action of the PMSG. • These accessory corpora lutea produce progestogens important to the maintenance of pregnancy in the mare. • A single injection of PMSG has biologic effects on the target gland for more than a week.

  46. Human Chorionic GonadotropinhCG • It is synthesized by the syncytiotrophoblastic cells of the placenta of primates, and it is found in both the blood and urine. • It is detected in the urine 8 days after conception by sensitive radio-immunoassays. • The LH-like action of hCG has made it the first hormone available for treatment of cystic ovaries in cattle. The hCG treatment of a cow with cystic ovaries usually requires 5,000 to 10,000 IU of hCG, after which the follicle either ovulates and forms a corpus luteum or more often, luteinizes. • In either cases, the luteal structure produces progesterone and the corpus luteum is functional for 20 days and regresses normally, allowing the cow to cycle 21 days after treatment.

  47. 4-6 Reproductive Role of Prostaglandins • Prostaglandins are a group of biologically active lipids that have arachidonic acid, a 20-carbon, unsaturated fatty acid as their precursor. • While prostaglandins have hormone-like actions, they do not fit the classic definition of a hormone. They are not produced by a specific gland or tissue. Rather, they are produced by cells throughout the body including cells in the uterus (female) and vesicular glands *male). • In most cases they act locally at the site of their production, but in some cases their site of action is in another tissue or organ. • Prostaglandins are rapidly degraded in mammals with about 90% of their activity lost in one passage through the pulmonary circulation. • Based on differences in chemical structure several parent prostaglandin compounds have been identified. Of these, prostaglandin E series (PGE) and prostaglandin F series (PGF) are of greatest biological interest. The two compounds most closely associated with reproduction are PGF2α and PGE2 (Figure 4-6)

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