Biomedical Engineering Reference
In-Depth Information
FSH exerts its molecular effects via a specifi c receptor on the surface of sensitive cells. This
receptor contains a characteristic seven transmembrane-spanning regions and is functionally cou-
pled (via membrane-associated G-proteins) to adenylate cyclase. This generates the second mes-
senger cAMP. FSH itself can promote increased expression of its own receptor in the short term,
although longer-term exposure to elevated FSH levels down-regulates receptor numbers. Cloning
and analysis of gonadotrophin receptors from several species indicate a high level of homology
between the FSH, LH and CG receptors.
LH exhibits a molecular mass of 28.5 kDa. The gene coding for the β-subunit of this glycopro-
tein hormone is present on human chromosome 19. This subunit exhibits signifi cant amino acid
homology to placental CG. Both promote identical biological effects and act via the same 93 kDa
cell surface receptor. The LH receptor is present on testicular Leydig cells in males and on female
ovarian theca, as well as granulosa, luteal and interstitial cells.
LH promotes synthesis of testosterone, the major male androgen (Box 11.5) by the testicular
Leydig cells. FSH sensitizes these cells to the activities of LH, probably by increasing LH receptor
numbers on the cell surface. Leydig cells have a limited storage capacity for testosterone (
∼
25
µ
g),
but secrete 5-10 mg of the hormone into the bloodstream daily in young healthy males.
The primary cellular targets of LH in the females are the follicular theca cells, which con-
stitutively express the LH receptor. Under the infl uence of LH, these cells produce androgens.
The androgens (principally testosterone) are then taken up by granulosa cells and converted into
oestrogens (Box 11.5) by the already-mentioned aromatase complex. Thus, the follicle represents
the major female gonadal endocrine unit, in which granulosa and theca cells cooperate in the
synthesis of oestrogens. Physiologically, LH in the female plays a major role in maturation of the
dominant follicle and appears central to triggering ovulation.
11.5.2 Pregnant mare serum gonadotrophin
Pregnant mare serum gonadotrophin (PMSG) is a unique member of the gonadotrophin family of
hormones. It is synthesized only by pregnant mares (i.e. is not found in other species). Further-
more, it displays both FSH-like and LH-like biological activities.
This glycoprotein hormone is a heterodimer, composed of an α and a β subunit and approxi-
mately 45 per cent of its molecular mass is carbohydrate. Reported molecular masses range from
52 to 68 kDa, a refl ection of the potential variability of the hormone's carbohydrate content.
PMSG is secreted by cup-shaped outgrowths found in the horn of the uterus of pregnant horses.
These equine-specifi c endometrial cups are of foetal, rather than maternal, origin. They fi rst be-
come visible around day 40 of gestation, and reach maximum size at about day 70, after which
they steadily regress. They synthesize high levels of PMSG and secrete it into the blood, where it
is detectable between days 40 and 130 of gestation.
11.5.3 The inhibins and activins
The inhibins and activins are a family of dimeric growth factors synthesized in the gonads. They
exert direct effects both on gonadal and extra-gonadal tissue, and are members of the TGF-β
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