Steroid Hormone Disorders and Pregnancy

Question 1

hCG

Answer 1

Stimulation of corpus luteum by hCG to maintain oestradiol and progesterone secretion
- hCG peaks at 2nd month of gestation

Inadequate secretion of hCG by syncytiotrophoblast leads to abortion

Production of progesterone and oestrogen is later taken over by the feto-placental unit

Question 2

Feto-Placental Unit

Answer 2

Foetal ACTH stimulates fetal adrenal zone in the adrenal glands –> produces DHEAS which is transported to placenta directly or via liver (with hydroxylation)

Sulphatase enzyme in the placenta cleaves sulphate from DHEAS to yield DHEA which are then aromatised to form E1/2/3/4
–> E3 predominant (oestriol)

Rising levels of oestrogens (esp oestriol) in maternal urine = well-being of feta-placental unit
- anencephalic foetuses or women with rare X-linked placental sulphatase deficiency –> oestrogens don’t rise and women fail to go into labour

Outcomes:

• anencephalic infants die soon after birth
• PSD males are born healthy but develop skin condition called ichthyosis (scaly skin)

Question 3

Initiation of Labour

Answer 3

Oestrogens and progesterone mutually oppose each other

• oestrogens promote uterine contractility whereas progesterone opposes it
• deficient oestrogens = less contraction = prolong pregnancy

==> towards term, steroid hormones rapidly decrease which initiates parturition process (less inhibition by progesterone –> PGs increase contraction)

Question 4

Male sexual differentiation

Answer 4

Male: androgens required
Default development is female phenotype with stimulation from ovarian oestrogens

SRY gene –> testis determining protein initiates differentiation of gonadal medullar into primordial testis

Testosterone from primordial leydig cells–> development of Wolffian ducts into internal male sex ducts and masculinisation of external genitalia (via DHT)

Mullerian inhibitory factor from Sertoli cells causes regression of mullerian duct which develops into internal sex organs in females

Sexual differentiation completes before end of 1st trimester (assuming XY genotype and intact androgen receptors)

Question 5

Testicular Feminisation Syndrome causes, manifestations, treatment

Answer 5

Female phenotype in a genetic male (XY)

Causes:

• defective androgen receptor i.e. ANDROGEN INSENSITIVITY syndrome (testosterone can’t exert phenotypic and feedback effects –> HIGH TESTOSTERONE with LH/FSH NOT SUPPRESSED)
• -> varying severities (incomplete = ambiguous genitalia with earlier Dx; complete = like female with later Dx)
• 17 alpha hydroxylase deficiency (rare) – no cleavage to side chain to yield steroid precursors; HYPERTENSION due to increased mineralocorticoid synthesis, LOW TESTOSTERONE
• 5 alpha reductase deficiency “girls who turn into boys after puberty” –> large amounts of testosterone after puberty = can masculinise external genitalia
  (undiagnosed until menarche is expected – primary amenorrhea, virilisation, masculinisation)

Treatment of androgen insensitivity:

• Gonads should be removed to prevent neoplasm from excessive stimulations from raised gonadotrophins
• Administer exogenous oestrogens

Question 6

Glucocorticoids and Respiratory Distress Syndrome

Answer 6

Premature infants <32 wks
Lungs lack surfactant (90% lecithin) which normally rise after 32 wks
–> assess maturity of lungs by measuring ratio of lecithin to sphingomyelin in amniotic fluid (<1.5 = high risk of RDS)

Normal maturation of lungs relies on secretion of glucocorticoids in the last few wks of pregnancy

Question 7

Antisteroids

Answer 7

Steroid hormone receptor blockers which block biological actions

Inhibitors of steroid hormone synthesis which blocks key enzymes in final synthesis of active steroid

Need for anti steroids:

• natural steroids for survival –> action on cytoplasmic receptors which translocate to nucleus and activate genes –> can go astray and cause problems
• many steroid are anabolic agents –> growth promotion may lead to carcinogenesis

Question 8

Anti-Androgens

Answer 8

Androgen antagonists

• Danazol (endometriosis)
• Finasteride [5 alpha reductase inhib] (baldness, CA prostate)

“Chemical castrants” for aberrant sexual behaviour and androgen dependent cancers e.g. CA prostate
- cyproterone (blocks receptors)
- cyproterone acetate
(also causes atrophy of adrenal glands and adrenal insufficiency)

Effects:
- exogenous androgens suppresses endogenous LH and FSH –> reduce intratesticular concentration of testosterone –> testes shrink!

Question 9

Anti-Oestrogens and Progesterones

Answer 9

Anti-oestrogens:
Clomiphene in ovulation induction (block negative feedback inhibition of estradiol on FSH secretion)

Tamoxifen in oestrogen dependant cancers e.g. CA breast

Anti-progesterones:
- Mifepristone (cause contractility of uterus for “morning after” abortion pill)