Biomedical Engineering Reference
In-Depth Information
Most superovulatory regimes utilizing p-FSH entail its administration to the recipient animal
twice daily for 4-5 days. Regular injections are required due to the relatively short half-life of FSH
in serum; s.c. administration helps prolong the duration of effectiveness of each injection. The 4
or 5 days of treatment with FSH is followed by a single dose of LH, promoting fi nal follicular
maturation and ovulation.
The causes of variability of superovulatory responses are complex and not fully understood.
The general health of the animal, as well as its characteristic reproductive physiology, is impor-
tant. The exact composition of the gonadotrophin preparations administered and the exact admin-
istration protocol also infl uence the outcome. The variability of FSH:LH ratios in many p-FSH
preparations can affect the results obtained, with the most consistent superovulatory responses
being observed when FSH preparations exhibiting low LH activity are used. The availability of
recombinant FSH and LH will overcome these diffi culties at least.
An alternative superovulatory regime entails administration of PMSG, which, as described ear-
lier, exhibits both FSH and LH activity. The major rationale for utilizing PMSG is its relatively long
circulatory half-life. In cattle, clearance of PMSG may take up to 5 days. The slow clearance rate
appears to be due to the molecule's high content of
N
-acetyl-neuramic acid. This extended serum
half-life means that a single dose of PMSG is suffi cient to induce a superovulatory response. Para-
doxically, however, its extended half-life limits its use in practice. Post-ovulatory stimulation of fol-
licular growth can occur, resulting in the recovery of a reduce number of viable embryos. Attempts
to negate this biological effect have centred around administration of anti-PMSG antibodies several
days after PMSG administration. However, this gonadotrophin is still not widely used.
11.7 Additional recombinant hormones now approved
Three additional recombinant hormones have recently gained marketing approval: thyroid-stimu-
lating hormone, parathyroid hormone and calcitonin.
Structurally, thyroid-stimulating hormone (TSH or thyrotrophin) is classifi ed as a member of
the gonadotrophin family, although functionally it targets the thyroid gland as opposed to the
gonads. As with other gonadotrophins, it is a heterodimeric glycoprotein displaying a common
α-subunit and a unique β-subunit. The β-subunit shows less homology to that of other members of
the group. It consists of 118 amino acids, is particularly rich in cysteine residues and contains one
N-linked glycosylation site (Asn 23).
TSH is synthesized by a distinct pituitary cell type: the thyrotroph. Its synthesis and release are
promoted by thyrotrophin-releasing hormone (a hypothalamic tripeptide hormone). TSH exerts
its characteristic effects by binding specifi c receptors found primarily, but not exclusively, on the
surface of thyroid gland cells. Binding to the receptor activates adenylate cyclase, leading to in-
creased intracellular cAMP levels. Ultimately, this triggers TSH's characteristic effects on thyroid
function, including promoting iodine uptake from the blood, synthesis of the iodine-containing
thyroid hormones thyroxine (T
4
) and triiodothyronine (T
3
) and the release of these hormones into
the blood, from where they regulate many aspects of general tissue metabolic activity. Elevated
plasma levels of T
4
and T
3
also promote decreased TSH synthesis and release by a negative feed-
back mechanism.
TSH is approved for medical use as a diagnostic aid in the detection of thyroid cancer/thyroid
remnants in post-thyroidectomy patients. Thyroid cancer is relatively rare, exhibiting highest
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