ENDOCRINOLOGY in ENDOCRINOLOGY in pregnancypregnancy

INTRODUCTIONINTRODUCTION

The synthesis and role of hormones in The synthesis and role of hormones in pregnancy is a unique interplay between pregnancy is a unique interplay between the three major compartments of the three major compartments of pregnancy: pregnancy: the fetus, the placenta, and the fetus, the placenta, and the motherthe mother. .

Some hormones are produced in the Some hormones are produced in the nonpregnant state and up regulated in nonpregnant state and up regulated in pregnancy (quantitative hormones), pregnancy (quantitative hormones), whereas others are largely unique to the whereas others are largely unique to the pregnant state (qualitative hormones). pregnant state (qualitative hormones).

contdcontd

Hormones for maturation of graffian Hormones for maturation of graffian follicle,ovulation,maintenance of corpus follicle,ovulation,maintenance of corpus luteum after fertilization.luteum after fertilization.

Placental endocrinology.Placental endocrinology. physiological alteration of endocrine glands physiological alteration of endocrine glands

(thyroid,pituitary,adrenal,parathyroid,&pancr(thyroid,pituitary,adrenal,parathyroid,&pancrease).ease).

Endocrine control of labour.Endocrine control of labour. Maintenance of lactation.Maintenance of lactation.

Maturation of graafian follicles& Maturation of graafian follicles& ovulationovulation

For GF maturation –mainly FSH & small For GF maturation –mainly FSH & small portion of LH,oestrogen.portion of LH,oestrogen.

For ovulation FSH & LH surge.For ovulation FSH & LH surge. After ovulation GF is changed to corpus After ovulation GF is changed to corpus

luteum.luteum. CL secretes –progesterone,17 CL secretes –progesterone,17 αα hydroxy hydroxy

progestrone,oestradiol,androstenedione(theprogestrone,oestradiol,androstenedione(theca cells).ca cells).

Maintenance of CL after Maintenance of CL after fertilizationfertilization

Needs progestrone ,hCG,hPL for growth Needs progestrone ,hCG,hPL for growth &function of CL.&function of CL.

Secreted by syncytiotrophoblast.Secreted by syncytiotrophoblast.

THE CORPUS LUTEUMTHE CORPUS LUTEUM

What happens in pregnancy ?What happens in pregnancy ?– hCG hCG for rescuing the corpus luteum for rescuing the corpus luteum– Synthesizes crucial hormones Synthesizes crucial hormones

Progesterone, estradiol, inhibin A, Progesterone, estradiol, inhibin A, relaxin, and VEGF relaxin, and VEGF

Functions of the hormonesFunctions of the hormones– Growth and development of the embryo Growth and development of the embryo – Inhibit spontaneous uterine activityInhibit spontaneous uterine activity– Suppress further folliculogenesisSuppress further folliculogenesis

PLACENTAL PLACENTAL ENDOCRINOLOGYENDOCRINOLOGY

At 6-8 wks there is transfer of function of At 6-8 wks there is transfer of function of corpus luteum to placenta.corpus luteum to placenta.

SyncitiotrophoblastsSyncitiotrophoblasts are the principal are the principal site of pituitary-like hormones & other site of pituitary-like hormones & other protein and steroid hormones where as protein and steroid hormones where as hypothalamic- like hormones are hypothalamic- like hormones are localized to thelocalized to the cytotrophoblastic layer cytotrophoblastic layer

PLACENTAL HORMONESPLACENTAL HORMONES

Hypothalamic like hormonesHypothalamic like hormones– CRHCRH– GnRHGnRH– TRH (thyrotrophin releasing)TRH (thyrotrophin releasing)– GHRHGHRH

Pituitary like hormonesPituitary like hormones– ACTHACTH– hCGhCG– hCT (human chorionic thyrotrophin).hCT (human chorionic thyrotrophin).– hPLhPL

Cont…Cont…

Steroid hormonesSteroid hormones– Estrogen (oestriol)Estrogen (oestriol)– ProgesteroneProgesterone– CortisolCortisol

Growth factorsGrowth factors– InhibinInhibin– ActivinActivin– TGF- TGF- ,IGF 1& 2, EGF,IGF 1& 2, EGF

Cont…Cont…

Other pregnancy proteinsOther pregnancy proteins– PSPS-1G-1G– PAPP-APAPP-A– RelaxinRelaxin– ProlactinProlactin– Atrial natriuretic peptideAtrial natriuretic peptide– Early pregnancy factorEarly pregnancy factor

hCGhCGCharacteristics Characteristics

Produced by the Syncitiotrophoblasts Produced by the Syncitiotrophoblasts Glycoprotein of m.w. 36000 – 40000 DGlycoprotein of m.w. 36000 – 40000 D Consists of 2 subunits - Consists of 2 subunits - & & The The subunit is biochemically similar to LH, subunit is biochemically similar to LH,

FSH & TSH ;where as the FSH & TSH ;where as the subunit is subunit is relatively unique to hCGrelatively unique to hCG

Intraplacental regulatory system - GnRH Intraplacental regulatory system - GnRH stimulates hCG & Inhibin inhibit GnRH stimulates hCG & Inhibin inhibit GnRH release and there by hCG release. release and there by hCG release.

Functions of HCGFunctions of HCG

Rescue & maintenance of corpus luteum till 6 Rescue & maintenance of corpus luteum till 6 wks of pregnancywks of pregnancy

Stimulation of fetal testis Stimulation of fetal testis Immunosuppressive activityImmunosuppressive activity Stimulates both adrenal & placental Stimulates both adrenal & placental

steroidogenesissteroidogenesis Stimulates maternal thyroidStimulates maternal thyroid Promotes Relaxin secretion by corpus luteumPromotes Relaxin secretion by corpus luteum

Functions of HCGFunctions of HCG

Levels of hCG Levels of hCG

Detected in maternal serum or urine as early Detected in maternal serum or urine as early as 8 -9 days following ovulationas 8 -9 days following ovulation

Doubling time Doubling time 1.4 -2 days 1.4 -2 days Maximum level 100 – 200 IU / ml between 60 Maximum level 100 – 200 IU / ml between 60

-70 days of pregnancy-70 days of pregnancy Begin to decline at 10-12 wks, a nadir Begin to decline at 10-12 wks, a nadir

reached at 20 wks, thereafter maintained at reached at 20 wks, thereafter maintained at that levelthat level

Disappears from the circulation within 2 wks Disappears from the circulation within 2 wks following delivery. following delivery.

Cont…Cont… High levels are seen inHigh levels are seen in

– Multiple pregnancyMultiple pregnancy– Erythoblastosis fetalisErythoblastosis fetalis– Hydatidiform mole Hydatidiform mole – Choriocarcinoma Choriocarcinoma – Down syndromeDown syndrome

Lower levels are seen inLower levels are seen in– Ectopic pregnancyEctopic pregnancy– Impending spontaneous abortionImpending spontaneous abortion

HUMAN PLACENTAL HUMAN PLACENTAL LACTOGENLACTOGEN

Also known as human chorionic Also known as human chorionic somatomammotrophinsomatomammotrophin

Synthesized by syncitiotrophoblastsSynthesized by syncitiotrophoblasts Detected as early as 2Detected as early as 2ndnd/ 3/ 3rdrd wk after wk after

fertilization, rises steadily until about 34-36 fertilization, rises steadily until about 34-36 wks.(5wks.(5μμg-25µg/ml)g-25µg/ml)

Rate of secretion is proportional to placental Rate of secretion is proportional to placental massmass

Cont…Cont… Functions Functions – Lipolysis and increase in the levels of Lipolysis and increase in the levels of

circulating free fatty acids; there by circulating free fatty acids; there by providing a source of energy for maternal providing a source of energy for maternal metabolism & fetal nutritionmetabolism & fetal nutrition

– Favours protein synthesis & promotes Favours protein synthesis & promotes transport of amino acids & glucose to transport of amino acids & glucose to fetus.Potent angiogenic helps to develop fetus.Potent angiogenic helps to develop fetal vasculature.fetal vasculature.

– Antagonises insulin action,promotes Antagonises insulin action,promotes growth of breast.growth of breast.

Other protein hormonesOther protein hormones Pregnancy specific Pregnancy specific ββ-1 glycoprotein (PS -1 glycoprotein (PS ββ-1G)--1G)-

produced by trophoblast cells.produced by trophoblast cells. Dected in maternal serum 18-20days after Dected in maternal serum 18-20days after

ovulation.ovulation. Potent immunosuppressor of lymphocyte Potent immunosuppressor of lymphocyte

proliferation & prevents rejection of the proliferation & prevents rejection of the conceptus.conceptus.

Early pregnancy factor (EPF) –dectectable in Early pregnancy factor (EPF) –dectectable in circulation 6-24 hrs after conception.circulation 6-24 hrs after conception.

Is a immuno suppressant &prevent rejection of Is a immuno suppressant &prevent rejection of conceptus.conceptus.

PAPP-A –secreted by PAPP-A –secreted by syncytiotrophoblast.immunosuppressant.syncytiotrophoblast.immunosuppressant.

ESTROGENESTROGENE1 is the predominant estrogen in menopause.

E2 is the predominant estrogen secreted by the ovary.

E3 is almost exclusively produced in pregnancy by the placenta

ESTROGENESTROGEN Produced by syncitiotrophoblasts.placenta is Produced by syncitiotrophoblasts.placenta is

an incomplete endocrine organ,no capability an incomplete endocrine organ,no capability of independent steroidgenesis. of independent steroidgenesis.

Precursors are derived mainly from the fetal Precursors are derived mainly from the fetal & partly from maternal sources& partly from maternal sources

First detectable at 9 wks, increases First detectable at 9 wks, increases gradually up to termgradually up to term

Levels are decreased inLevels are decreased in– Fetal death, fetal anomalies.(down Fetal death, fetal anomalies.(down

syn,anencephaly,adrenal atrophy).syn,anencephaly,adrenal atrophy).– Hydatidiform moleHydatidiform mole– Placental sulphatase / aromatase Placental sulphatase / aromatase

deficiency deficiency

PROGESTERONEPROGESTERONE Plasma level gradually increases with Plasma level gradually increases with

pregnancy, decreases rapidly after delivery pregnancy, decreases rapidly after delivery & is not detectable 24 hrs after delivery& is not detectable 24 hrs after delivery

Lower progesterone levelLower progesterone level– Ectopic pregnancyEctopic pregnancy– AbortionAbortion

Higher levelHigher level– Hydatidiform moleHydatidiform mole– Rh isoimmunisationRh isoimmunisation

Maternal-feto- placental unit Maternal-feto- placental unit for steroidgenesisfor steroidgenesis

Functions of E & PFunctions of E & P

Maintenance of pregnancyMaintenance of pregnancy– Hypertrophy & hyperplasia of myometrium - EHypertrophy & hyperplasia of myometrium - E– Stimulates growth of uterus, decidual changes Stimulates growth of uterus, decidual changes

& inhibits myometrial contraction - P& inhibits myometrial contraction - P Breast developmentBreast development

– Hypertrophy & proliferation of ducts – EHypertrophy & proliferation of ducts – E– Development of lobulo- alveolar system – E+PDevelopment of lobulo- alveolar system – E+P

Adaptation of maternal organs to the Adaptation of maternal organs to the constantly increasing demands of growing constantly increasing demands of growing fetusfetus

Cont…Cont…

Estrogen Estrogen – Sensitizes myometrium to Oxytocin & Sensitizes myometrium to Oxytocin &

prostaglandinsprostaglandins– Ripens the cervixRipens the cervix

ProgesteroneProgesterone– Along with hCG & decidual Cortisol Along with hCG & decidual Cortisol

inhibits T-lymphocyte mediated tissue inhibits T-lymphocyte mediated tissue rejectionrejection

DIAGNOSTIC VALUE OF DIAGNOSTIC VALUE OF PLACENTAL HORMONESPLACENTAL HORMONES Diagnosis of pregnancy.(presence of Diagnosis of pregnancy.(presence of

hCG in serum & urine by RIA.).hCG in serum & urine by RIA.).

Follow up of GTT casesFollow up of GTT cases

Detection of fetal anomalies.Detection of fetal anomalies.

RelaxinRelaxin

Produced by CL,placenta, decidua.Produced by CL,placenta, decidua. Related to insulin.peptide hormone.Related to insulin.peptide hormone. Relaxes myometrium,the symphysis & Relaxes myometrium,the symphysis &

sacroiliac joints during pregnancy and helps sacroiliac joints during pregnancy and helps in cervical ripening.in cervical ripening.

Changes of endocrine glands Changes of endocrine glands during pregnancyduring pregnancy

To adjust the internal environment of the To adjust the internal environment of the mother to meet the additional requirement mother to meet the additional requirement imposed by metabolic changes & extra imposed by metabolic changes & extra demand by the growing foetus.demand by the growing foetus.

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Changes of endocrine glands Changes of endocrine glands glandgland morphologicamorphologica

llphysiologicalphysiological

pituitarypituitary increase in increase in weight by 30-weight by 30-50%.twice in 50%.twice in sizesize

↑↑GH,prolatin,ACTH &CRH.normal GH,prolatin,ACTH &CRH.normal TSH & ↓ed gonadotrophin.TSH & ↓ed gonadotrophin.

thyroidthyroid HyperplasiaHyperplasia Maternal serum iodine Maternal serum iodine ↓,↓,↑BMR.↑↑BMR.↑TBG,TBG,↑total T3 &T4 but ↑total T3 &T4 but freeT3,T4 &TSH unchangedfreeT3,T4 &TSH unchanged

adrenal adrenal cortexcortex

minimal minimal enlargementenlargement

↑↑ed ed Aldosterone,DOC(deoxycorticosteronAldosterone,DOC(deoxycorticosterone),CBG,Cortisol &free cortisole),CBG,Cortisol &free cortisol

parathyroidparathyroid HyperplasiaHyperplasia PTH normal ,does not cross PTH normal ,does not cross placenta.placenta.

pancreaspancreas Hyper Insulinism in 3Hyper Insulinism in 3rdrd trimester.anti- trimester.anti-insulin factors & insulin resistance insulin factors & insulin resistance modify action of insulin during preg.modify action of insulin during preg.

Thyroid glandThyroid gland Hyperplasia & slight generalised enlargement Hyperplasia & slight generalised enlargement

of gland.of gland. Maternal serum iodine level fall due to Maternal serum iodine level fall due to ↑ed ↑ed

renal loss & trans placental shift to fetus.renal loss & trans placental shift to fetus. Iodine intake increased from 100-150µgm/day to Iodine intake increased from 100-150µgm/day to

200µg/day.200µg/day. Rise in BMR due to↑ed maternal &fetal oxygen Rise in BMR due to↑ed maternal &fetal oxygen

need.need. ↑↑ed serum protein bound iodine& thyroxin bound ed serum protein bound iodine& thyroxin bound

globulin due to oestrogen stimulation.globulin due to oestrogen stimulation. Total T3 ,T4↑ed but free T3,T4 &TSH remain Total T3 ,T4↑ed but free T3,T4 &TSH remain

normal.normal.

Contd.Contd. Level of calcitonin Level of calcitonin ↑ed by 20%.↑ed by 20%. Since increase in TBG dependent on Since increase in TBG dependent on

oestrogen ,a failure of the PBI to rise indicate oestrogen ,a failure of the PBI to rise indicate fetal compromise.fetal compromise.

Adrenal cortex—slight enlargement of adrenal Adrenal cortex—slight enlargement of adrenal cortex (thickness of zona fasciculata ↑ed).cortex (thickness of zona fasciculata ↑ed).

Significant ↑ed in aldosterone, deoxy Significant ↑ed in aldosterone, deoxy corticosterone(DOC) corticosteroid binding corticosterone(DOC) corticosteroid binding globulin (double), cortisol & free cortisol .globulin (double), cortisol & free cortisol .

Hypercortisolism occure due to ↑ed plasma Hypercortisolism occure due to ↑ed plasma cortisol half life, delayed plasma clearance by cortisol half life, delayed plasma clearance by kidney resetting of H-P-adrenal feedback kidney resetting of H-P-adrenal feedback mechanism.mechanism.

Stages of lactationStages of lactation

Mammogenesis– preparation of breast.Mammogenesis– preparation of breast. Lactogenesis– synthesis & secretion of milk Lactogenesis– synthesis & secretion of milk

by breast alveoli.by breast alveoli. Galactokinesis– ejection of milk.Galactokinesis– ejection of milk. Galactopoiesis—maintenance of lactation. Galactopoiesis—maintenance of lactation.

Hormone responsible for Hormone responsible for lactationlactation