Endocrinology
Content
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INTRODUCTION The endocrine system is made up of glands that produce and secrete hormones, chemical substance produce in the body that regulates the activity of cells or organs. These hormones regulate the body growth, metabolism and sexual development and function. The hormones are released in to the blood stream and may affect one or several organs throughout the body. Hormones are chemical messengers created by the body. They transfer information from one set of cells to another to co-ordinate the function of different parts of the body The major glands of the endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenals, pineal bodies and the reproductive organs (ovaries and testes). The pancreas is also a part of this it has a role in hormone production as well as in digestion. ENDOCRINOLOGY Endocrinology is a branch of biology and medicine dealing with the endocrine system, its disease, and its specific secretion called Hormones. Endocrinology is concerned with the study of the biosynthesis, storage, chemistry and physiologic function of hormones and with the cells of the endocrine glands and tissue that secrete them. ENDOCRINOLOGY IN RELATED TO REPRODUCTION The endocrine glands plays very important role in the physiology of reproduction. Endocrinology in relation to reproduction includes the knowledge of: Hormones essential for the maturation of the Graafian follicle. Ovulation and maintenance of Corpus Luteum after fertilization. Following conception, transfer of function of Pituitary-Ovarian axis to powerhouse or endocrine organ. During pregnancy, physiological alteration of various endocrine glands namely the pituitary, thyroid, parathyroid, adrenal and pancrease. Endocrine control of labour. Hormonal influence during puerperium necessary for maintenance of lactation.
MATURATION OF GRAAFIAN FOLLICLES AND OVULATION Follicular maturation takes place during the first half of the cycle. The hormones essential for follicular maturation are mainly FSH and a small portion of LH.
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OVULATION Under the influence of FSH about 20 Graafian Follicles develop and only one of them will be able to ovulate. The rest become atretic, mix up with interstitial tissues and acquires the potentiality to produce hormones. Causes of ovulation:Factors involved in ovulation are: Endocrinal L.H surge-sustained peak of oestrogen for 24-36 hours in the late follicular phase LH surge from anterior pituitary. Ovulation approximately occurs 16-24 hours after the LH surge.LH peak persisk for about 24 hours FSH rise-preovulatory rise of progenterone facilitates the positive feedback action of oestrogen to induce FSH surge increase in plasminogen activator Plasmin helps lysis of the wall of the follicle Thus the combined LH/FSH midcycle surge is responsible for the final stage of maturation rupture of the follicle and expulsion of the oocytes
CHANGES WITHIN THE FOLLICLE AFTER OVULATION The avascular graafian follicle becomes vascularised and the granulose cells become luteinised.The morphologically altered graffion follicle is now changed into corpusluteum. the corpus luteum secretes progesterone,17α hydroxy progesterone and oestradiol, androstenodione MAINTENANCE OF CORPUS LUTEUM AFTER FERTILIZATION Functions of corpusluteum is essential to maintenance of the early pregnancy. Corpus luteum secretes about 40mg of progesterone a day. After implantation human chorionic gonadotrophin (hcg) and possible placental lactogen (hpl) secreted by the syncytiotrophoblast cells maintains the growth and functions of the corpus luteum. PLACENTAL ENDOCRINOLOGY At 6-8 weeks there is transfer of functions of Corpus luteum to the placenta which acts temporarily as a new endocrine organ or power house of hormone production.
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HORMONES OF PLACENTA Placenta produces a variety of hormones of which protein and steroid hormones are significantly important. Syncytiotrophoblasts are the principle site of protein and steroid hormones in pregnancy. I. Protein hormones: Protein hormones are similar but not necessarily identical with those produce by the pituitary. a) Human Chorionic Gonadotrophin (HCG) HCG is a glycoprotein. It consist of a hormone non-specific α (92 amino acids) and a hormone specific β(145 aminoacids) subunit. HCG is chemically and functionally similar to pituitary luteinizing hormone. Functions: It acts as a stimulus for the secretion of progesterone by the corpusluteum of pregnancy. HCG stimulates Leydig cells of the male fetus to produce testosterone. It is thus indirectly involved in the development of male external genitalia. It has got immuno-suppressive activity which may inhibit the maternal process of immunorejection of the fetus as a homograft. Stimulates both adrenal and placental steroidogenesis. Stimulates maternal thyroid because of its thyrotrophic activity.
b) Human Placental Lactogen (HPL) This is also known as human chorionic somatomammotrophin (HCS). This hormone is synthesized by the syncytiotrophoblast of the placenta . The hormones is clinically and immunologically similar to pituitary growth hormone and plolactin. Function o HPL antagonizes insulin action. o High level of maternal insulin helps protein synthesis. o HPL causes lipolysis and proteolysis and promote transfer of glucose and aminoacid to the fetus.
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c) Pregnancy specific B-1 Glycoprotein (PS B-1G) It is protected by the trophoblast cells. It can be detected in the maternal serum 18-20 days after ovulation. d) Early pregnancy factor (EPF) It is a protein, produce by the activate platelets and other maternal tissue. It is detectable in the circulation 6-24hours after conception. EPF is immune-suppressor of lymphocyte proliferation and prevents rejection of the conceptus. e) Growth factor Inhibin, activin, insulin like growth factor (1GF-1 and 2), transforming growth factor B(TGF-B) and Epidermal growth factor (EGF) are produced by syncytiotrophoblast cells. They have varied functions including immunosuppressive, paracrine and steroidogenic. f) Pregnancy associated plasma protein(PAPP-A) A PAPP is secreted by the syncytiotrophoblast. It acts as an immunosuppressant in pregnancy.
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STEROIDAL HORMONES a) Oestrogen : In late pregnancy, qualitatively, oestriol is the most important amongst the three major oestrogens. The site of its production is in the syncytiotrophoblast. Oestriol is first detected at 9 weeks and increase gradually to about 30ng/ml at term. Fetal death, fetal anomalies, hydatidiform mole, placental sulphatase or aromatase deficiency are associated with low oestriol. b) Progesterone : Before 6 weeks of pregnancy, the corpus luteum secretes 17hydroxy progesterone. Following the development of trophoblast, progesterone is synthesized and secreted in increasing amount from placenta. The average level of plasma progesterone at 12th week, 28th week and term approximate
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25ng/ml, 80ng/ml and 300ng/ml respectively. Low progesterone level are observed in ectopic pregnancy and in abortion. High values are observed in hydatidiform mole, Rhisoimmunisation. After delivery the plasma progesterone decreases rapidly and is not detectable after 24hours. Functions of the steroid hormones (oestroges and progesterone) It is indeed difficult to single out the function of one from the other. Oestrogen causes hypertrophy and hyperplasia of the uterine myometrium, thereby increasing the accommodation capacity and blood flow of the uterus progesterone in conjunction with oestrogen stimulates growth of the uterus, causes decidual changes of the endometrium required for implantation and it inhibits myometrial contraction. Hypertrophy and proliferation of the duct are due to estrogen, while those of lobulo-alveolar system are due to combined action of estrogen and progesteron. Both the steroids are required for the adaptation of the maternal organs to the constantly increasing demands of the growing fetus. Progesterone maintains uterine quiescence by stabilizing lysosomal membranes and inhibiting prostaglandin synthesis. Progesterone and oestrogens are antagonistic in the process of labor. Oestrogen sensitizes the myometrium to oxytocin and prostaglandins. Oestrogens ripen the cervix. Progesterone along with HCG and decidual cortisol inhibit Tlymphocyte mediated tissue rejection and protects the concepts. Together they causes inhibition of cyclic fluctuating activity of gonadotrophin-gonadal axis therby preserving gonadal function.
CHANGES OF ENDOCRINE GLANDS DURING PREGNANCY 1. Pituitary glands: Morphological changes in normal pregnancy: during normal pregnancy, the pituitary increase in weight by 30-50% and is enlarge to about twice its normal size. This is due to the
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hyperplasia of acidophilic prolactin secreting cells. Maternal pituitary glands is not necessary for the maintenance of pregnancy. Physiological changes: Pituitary gonadotrophin level are low due to increased level of estrogens and progesterone. Growth hormone level is elevated due to growth hormone variant made by syncytiotrophoblast of the placenta. Serum prolactin level increased by 10 times. TSH secretion is same as in nonpregnant state. ACTH and corticotrophin releasing hormone (CRH) level increase.
2. Thyroid glands: Morphological changes: hyperplasia of the thyroid glands and slight generalized enlargement of the gland. Physiological changes: Renal clearance of iodine is increased due to increased glomerular filteration. Maternal serum iodine level full due to increased renal loss and also due to transplantal shift to the foetus. There is rise in the basal metabolic rate. 3. Adrenal glands: Morphological changes: there is slight enlargement of the adrenal cortex, particularly the thickness of the zona fasiculata is increased. Physiological changes: there is significant increase in the serum level of aldosterone, deoxycorticosterone(DOC), corticosteroid binding globulin (CBG), cortisol and free cortisol. 4. The Parathyroid glands Morphological changes : maternal Parathyroid hyperplasia. Physiological changes : concentration of parathyroid hormone(PTH). 5. The Pancrease
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Physiological changes : there is hyperinsulinism particularly during third trimester which is due to the peak concentration of placental hormones.
ENDOCRINE CONTROL OF ONSET OF LABOR Theories regarding initiation of labor include the following: Oxytocin stimulates theory : Although the mechanism is unknown, the uterus become increasingly sensitive to oxytocin as the pregnancy progresses. Estrogen stimulation theory: Estrogen stimulates irritability of uterine muscle and enhance uterine contraction. Progesterone withdrawal theory: A decrease in progesterone production may stimulate prostaglandin(PG) synthesis and enhance the effect of estrogen, which has a stimulating effects on uterine muscles. Fetal cortisol theory : Cortisol may affect maternal estrogen levels. Prostaglandin stimulation theory: prostaglandin stimulates smooth muscle to contract.
HORMONE INFLUENCES NECESSARY FOR MAINTENANCE OF LACTATION The breast is a modified sweat gland. It consists of ducts, alveoli and fibrofatty connective tissue. During puberty there is proliferation of fibrofatty tissue, without any changes in the alveoli ductal system. The endocrine control of lactation can be divided into following stages. a) b) c) d) Mammogenesis: preparation of breast. Lactogenesis : synthesis and secretion of milk by breast alveoli. Galactokinesis : Ejection of milk. Galactopoiesis : Maintenance of lactation.
INTRODUCTION The endocrine system is made up of glands that produce and secrete hormones, chemical substance produce in the body that regulates the activity of cells or organs. These hormones regulate the body growth, metabolism and sexual development and function. The hormones are released in to the blood stream and may affect one or several organs throughout the body. Hormones are chemical messengers created by the body. They transfer information from one set of cells to another to co-ordinate the function of different parts of the body The major glands of the endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenals, pineal bodies and the reproductive organs (ovaries and testes). The pancreas is also a part of this it has a role in hormone production as well as in digestion. ENDOCRINOLOGY Endocrinology is a branch of biology and medicine dealing with the endocrine system, its disease, and its specific secretion called Hormones. Endocrinology is concerned with the study of the biosynthesis, storage, chemistry and physiologic function of hormones and with the cells of the endocrine glands and tissue that secrete them. ENDOCRINOLOGY IN RELATED TO REPRODUCTION The endocrine glands plays very important role in the physiology of reproduction. Endocrinology in relation to reproduction includes the knowledge of: Hormones essential for the maturation of the Graafian follicle. Ovulation and maintenance of Corpus Luteum after fertilization. Following conception, transfer of function of Pituitary-Ovarian axis to powerhouse or endocrine organ. During pregnancy, physiological alteration of various endocrine glands namely the pituitary, thyroid, parathyroid, adrenal and pancrease. Endocrine control of labour. Hormonal influence during puerperium necessary for maintenance of lactation.
MATURATION OF GRAAFIAN FOLLICLES AND OVULATION Follicular maturation takes place during the first half of the cycle. The hormones essential for follicular maturation are mainly FSH and a small portion of LH.
2
OVULATION Under the influence of FSH about 20 Graafian Follicles develop and only one of them will be able to ovulate. The rest become atretic, mix up with interstitial tissues and acquires the potentiality to produce hormones. Causes of ovulation:Factors involved in ovulation are: Endocrinal L.H surge-sustained peak of oestrogen for 24-36 hours in the late follicular phase LH surge from anterior pituitary. Ovulation approximately occurs 16-24 hours after the LH surge.LH peak persisk for about 24 hours FSH rise-preovulatory rise of progenterone facilitates the positive feedback action of oestrogen to induce FSH surge increase in plasminogen activator Plasmin helps lysis of the wall of the follicle Thus the combined LH/FSH midcycle surge is responsible for the final stage of maturation rupture of the follicle and expulsion of the oocytes
CHANGES WITHIN THE FOLLICLE AFTER OVULATION The avascular graafian follicle becomes vascularised and the granulose cells become luteinised.The morphologically altered graffion follicle is now changed into corpusluteum. the corpus luteum secretes progesterone,17α hydroxy progesterone and oestradiol, androstenodione MAINTENANCE OF CORPUS LUTEUM AFTER FERTILIZATION Functions of corpusluteum is essential to maintenance of the early pregnancy. Corpus luteum secretes about 40mg of progesterone a day. After implantation human chorionic gonadotrophin (hcg) and possible placental lactogen (hpl) secreted by the syncytiotrophoblast cells maintains the growth and functions of the corpus luteum. PLACENTAL ENDOCRINOLOGY At 6-8 weeks there is transfer of functions of Corpus luteum to the placenta which acts temporarily as a new endocrine organ or power house of hormone production.
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HORMONES OF PLACENTA Placenta produces a variety of hormones of which protein and steroid hormones are significantly important. Syncytiotrophoblasts are the principle site of protein and steroid hormones in pregnancy. I. Protein hormones: Protein hormones are similar but not necessarily identical with those produce by the pituitary. a) Human Chorionic Gonadotrophin (HCG) HCG is a glycoprotein. It consist of a hormone non-specific α (92 amino acids) and a hormone specific β(145 aminoacids) subunit. HCG is chemically and functionally similar to pituitary luteinizing hormone. Functions: It acts as a stimulus for the secretion of progesterone by the corpusluteum of pregnancy. HCG stimulates Leydig cells of the male fetus to produce testosterone. It is thus indirectly involved in the development of male external genitalia. It has got immuno-suppressive activity which may inhibit the maternal process of immunorejection of the fetus as a homograft. Stimulates both adrenal and placental steroidogenesis. Stimulates maternal thyroid because of its thyrotrophic activity.
b) Human Placental Lactogen (HPL) This is also known as human chorionic somatomammotrophin (HCS). This hormone is synthesized by the syncytiotrophoblast of the placenta . The hormones is clinically and immunologically similar to pituitary growth hormone and plolactin. Function o HPL antagonizes insulin action. o High level of maternal insulin helps protein synthesis. o HPL causes lipolysis and proteolysis and promote transfer of glucose and aminoacid to the fetus.
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c) Pregnancy specific B-1 Glycoprotein (PS B-1G) It is protected by the trophoblast cells. It can be detected in the maternal serum 18-20 days after ovulation. d) Early pregnancy factor (EPF) It is a protein, produce by the activate platelets and other maternal tissue. It is detectable in the circulation 6-24hours after conception. EPF is immune-suppressor of lymphocyte proliferation and prevents rejection of the conceptus. e) Growth factor Inhibin, activin, insulin like growth factor (1GF-1 and 2), transforming growth factor B(TGF-B) and Epidermal growth factor (EGF) are produced by syncytiotrophoblast cells. They have varied functions including immunosuppressive, paracrine and steroidogenic. f) Pregnancy associated plasma protein(PAPP-A) A PAPP is secreted by the syncytiotrophoblast. It acts as an immunosuppressant in pregnancy.
II.
STEROIDAL HORMONES a) Oestrogen : In late pregnancy, qualitatively, oestriol is the most important amongst the three major oestrogens. The site of its production is in the syncytiotrophoblast. Oestriol is first detected at 9 weeks and increase gradually to about 30ng/ml at term. Fetal death, fetal anomalies, hydatidiform mole, placental sulphatase or aromatase deficiency are associated with low oestriol. b) Progesterone : Before 6 weeks of pregnancy, the corpus luteum secretes 17hydroxy progesterone. Following the development of trophoblast, progesterone is synthesized and secreted in increasing amount from placenta. The average level of plasma progesterone at 12th week, 28th week and term approximate
5
25ng/ml, 80ng/ml and 300ng/ml respectively. Low progesterone level are observed in ectopic pregnancy and in abortion. High values are observed in hydatidiform mole, Rhisoimmunisation. After delivery the plasma progesterone decreases rapidly and is not detectable after 24hours. Functions of the steroid hormones (oestroges and progesterone) It is indeed difficult to single out the function of one from the other. Oestrogen causes hypertrophy and hyperplasia of the uterine myometrium, thereby increasing the accommodation capacity and blood flow of the uterus progesterone in conjunction with oestrogen stimulates growth of the uterus, causes decidual changes of the endometrium required for implantation and it inhibits myometrial contraction. Hypertrophy and proliferation of the duct are due to estrogen, while those of lobulo-alveolar system are due to combined action of estrogen and progesteron. Both the steroids are required for the adaptation of the maternal organs to the constantly increasing demands of the growing fetus. Progesterone maintains uterine quiescence by stabilizing lysosomal membranes and inhibiting prostaglandin synthesis. Progesterone and oestrogens are antagonistic in the process of labor. Oestrogen sensitizes the myometrium to oxytocin and prostaglandins. Oestrogens ripen the cervix. Progesterone along with HCG and decidual cortisol inhibit Tlymphocyte mediated tissue rejection and protects the concepts. Together they causes inhibition of cyclic fluctuating activity of gonadotrophin-gonadal axis therby preserving gonadal function.
CHANGES OF ENDOCRINE GLANDS DURING PREGNANCY 1. Pituitary glands: Morphological changes in normal pregnancy: during normal pregnancy, the pituitary increase in weight by 30-50% and is enlarge to about twice its normal size. This is due to the
6
hyperplasia of acidophilic prolactin secreting cells. Maternal pituitary glands is not necessary for the maintenance of pregnancy. Physiological changes: Pituitary gonadotrophin level are low due to increased level of estrogens and progesterone. Growth hormone level is elevated due to growth hormone variant made by syncytiotrophoblast of the placenta. Serum prolactin level increased by 10 times. TSH secretion is same as in nonpregnant state. ACTH and corticotrophin releasing hormone (CRH) level increase.
2. Thyroid glands: Morphological changes: hyperplasia of the thyroid glands and slight generalized enlargement of the gland. Physiological changes: Renal clearance of iodine is increased due to increased glomerular filteration. Maternal serum iodine level full due to increased renal loss and also due to transplantal shift to the foetus. There is rise in the basal metabolic rate. 3. Adrenal glands: Morphological changes: there is slight enlargement of the adrenal cortex, particularly the thickness of the zona fasiculata is increased. Physiological changes: there is significant increase in the serum level of aldosterone, deoxycorticosterone(DOC), corticosteroid binding globulin (CBG), cortisol and free cortisol. 4. The Parathyroid glands Morphological changes : maternal Parathyroid hyperplasia. Physiological changes : concentration of parathyroid hormone(PTH). 5. The Pancrease
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Physiological changes : there is hyperinsulinism particularly during third trimester which is due to the peak concentration of placental hormones.
ENDOCRINE CONTROL OF ONSET OF LABOR Theories regarding initiation of labor include the following: Oxytocin stimulates theory : Although the mechanism is unknown, the uterus become increasingly sensitive to oxytocin as the pregnancy progresses. Estrogen stimulation theory: Estrogen stimulates irritability of uterine muscle and enhance uterine contraction. Progesterone withdrawal theory: A decrease in progesterone production may stimulate prostaglandin(PG) synthesis and enhance the effect of estrogen, which has a stimulating effects on uterine muscles. Fetal cortisol theory : Cortisol may affect maternal estrogen levels. Prostaglandin stimulation theory: prostaglandin stimulates smooth muscle to contract.
HORMONE INFLUENCES NECESSARY FOR MAINTENANCE OF LACTATION The breast is a modified sweat gland. It consists of ducts, alveoli and fibrofatty connective tissue. During puberty there is proliferation of fibrofatty tissue, without any changes in the alveoli ductal system. The endocrine control of lactation can be divided into following stages. a) b) c) d) Mammogenesis: preparation of breast. Lactogenesis : synthesis and secretion of milk by breast alveoli. Galactokinesis : Ejection of milk. Galactopoiesis : Maintenance of lactation.
