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Endocrinology in Relation to Reproduction

HORMONES OF PLACENTA:

Syncytiotrophoblasts are the principal site of protein and steroid hormones
Placenta produces a variety of hormones of which protein and steroid hormones

PROTEIN HORMONES:

HUMAN CHORIONIC GONADOTROPIN (hCG):

Glycoprotein.
LH-like activity
Hormone nonspecific α (identical to LH, TSH , FSH) and hormone specific β subunit

Functions:

Rescue and maintenance of corpus luteum till 6 weeks of pregnancy
Stimulates Leydig cells of the male fetus at 8 week to produce testosterone
Immunosuppressive activity
Diagnosis of hydatidiform mole
Stimulates both adrenal and placental steroidogenesis
Thyrotropic activity.
Promotes secretion of relaxin from the corpus luteum.

Abnormal rise in HCG:

Testicular embryonal tumors(Beta hCG)
Germ cell tumors
Extragonadal germinomas
Lung cancer
Yolk sac tumor
Hepatoma
Choriocarcinoma
Pancreatic islet tumors.
Down’s syndrome(Increased free beta HCG)
Minimum hCG level that a urine pregnancy test can detect is 5 m IU/ ml
Plasma levels of hCG during pregnancy doubles every 2 days

60 – 70 days of pregnancy	100-200 IU/mL
100 -130 days	10–20 IU/mL
32 weeks	100-200 IU/mL

HUMAN PLACENTAL LACTOGEN (hPL):

Human chorionic somatomammotropin
5 μg/mL to 25 μg/mL From 3rd week to 36 weeks of gestation
The plasma concentration of hPL is proportional to placental mass

Functions:

Antagonizes insulin
Maternal lipolysis
Promotes transfer of glucose and amino acids to the fetus
Angiogenic hormone
Growth and differentiation of breasts

PREGNANCY-SPECIFIC β-1 GLYCOPROTEIN (PS β-1G):

Detected in the maternal serum 18–20 days after ovulation
Immunosuppressor of lymphocyte proliferation and prevents rejection of the conceptus

Early pregnancy factor (EPF):

Immunosuppressant
Prevents rejection of the conceptus
Detectable in the circulation 6 – 24 hours after conception

Growth factors:

Inhibin
Activin
IGF-1 and 2
TGF-β
EGF
Functions
Immunosuppressive, paracrine and steroidogenic

Pregnancy-associated plasma protein—A (PAPP-A):

Immunosuppressant in pregnancy

STEROIDAL HORMONES:

ESTROGEN:

Site of its production :syncytiotrophoblast

Fetoplacental unit and biosynthesis of estriol:

Fetal adrenal gland and the placenta contain the complementary enzyme system
Estriol is first detectable at 9 weeks (0.05 ng/mL) and increases gradually to about 30 ng/mL at term.

Low estriol:

Fetal death
Fetal anomalies (adrenal atrophy, anencephaly, Down’s syndrome)
Hydatidiform moles
Placental sulfatase or aromatase deficiency

PROGESTERONE:

Before 6 weeks of pregnancy corpus luteum secretes 17-hydroxyprogesterone later by placenta.
250 mg/day

Low progesterone levels:

Ectopic pregnancy
Abortion

High values:

hydatidiform mole
Rh-isoimmunization.

Functions of the steroid hormones:

Estrogen:

Hypertrophy and hyperplasia of uterine myometrium
Hypertrophy and proliferation of ducts of breast
Sensitizes the myometrium to oxytocin and prostaglandin
Ripen the cervix.

Estrogen+Progesterone:

Growth of the uterus & decidual changes of the endometrium
Lobuloalveolar system
Adaptation of the maternal organs
Antagonistic in the process of labor
Preserve gonadal function.

Progesterone:

Maintains uterine quiescence
Immunomodulatory role

DIAGNOSTIC VALUE OF PLACENTAL HORMONES:

Diagnosis of pregnancy:

Presence of hCG:

Detected in the urine prior to the first missed period
RIA(most sensitive)
Biological

Follow-up cases who had trophoblastic tumors:

RIA for detection of hCG β subunit in hydatidiform mole or choriocarcinoma

Detection of function of fetoplacental unit:

Placental insufficiency and status of the fetus-in-utero are hPL and estriol

RELAXIN:

Produced from corpus luteum of the ovary, placenta and decidua
Relaxes myometrium, the symphysis and sacroiliac joints during pregnancy
Cervical ripening

CHANGES OF ENDOCRINE GLANDS DURING PREGNANCY:

GLAND	MORPHOLOGICAL	PHYSIOLOGICAL
PITUITARY GLAND	↑weight & size	↓FSH, LH ↑Growth hormone ↑Serum prolactin ↑ACTH and CRH
THYROID GLAND	Hyperplasia	↓Serum iodine ↑BMR Hyperthyroidism ↑Thyroxin-binding globulin ↑ Maternal total T4 and T3 Free T4 and T3 unchanged
ADRENAL CORTEX	Slight enlargement	↑aldosterone ↑DOC ↑CBG ↑ACTH ↑Cortisol ↑ CRH ↓ DHEAS ↑Testosterone ↑Androstenedione
PARATHYROID GLAND	Hyperplasia	↑1, 25 dihydroxy vitamin D levels ↑calcitriol
PANCREAS	Hypertrophy and hyperplasia	Hyperinsulinemia

HORMONAL INFLUENCES NECESSARY FOR MAINTENANCE OF LACTATION:

The endocrine control of lactation can be divided into following stages

Preparation of breast (mammogenesis
Synthesis and secretion of milk by breast alveoli(lactogenesis)
Ejection of milk (galactokinesis)
Maintenance of lactation (galactopoiesis)

Exam Important

Minimum level of HCG detected by radio immunoassay is 0.001 IU/ml
Abnormal rise of HCG in a female of reproductive age group may indicate Choriocarcinoma
Increased free beta HCG levels are features of down’s syndrome
Human chorionic gonadotropin produced by the human placenta has LH-like activity
Human chorionic somatotropin participates in stimulation of ductal growth in the mammary gland during pregnancy
HCG is glycoprotein
hCG can be detected in the urine prior to the first missed period
HCG titer, USG & Chest x ray are used for a diagnosis of hydatidiform mole
Radioimmune assay is the most sensitive or gold standard test for assessing HCG in maternal serum
Minimum hCG level that a urine pregnancy test can detect is 5 m IU/ ml
The corpus luteum of the ovary is maintained by the secretion of human chorionic gonadotropin from The trophoblast cells
HCG is secreted by Embryonal cell cancer,Yolk sac tumor, Choriocarcinoma & Polyembryoma
Placental HCG stimulates the gonads in male at 8 week to secret testosterone
Marker for testicular tumor is Beta hCG
During pregnancy, maximum urinary HCG level is reached in 70 days
Plasma levels of hCG during pregnancy doubles every 2 days
Alpha chain of HCG is identical to

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Endocrinology in Relation to Reproduction