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Background: The glycoproteic hormones, LH and FSH, circulate under heterogenous molecular forms, the isoforms. The more acidic isoforms of FSH are found in hypogonadic patients and a displacement towards the basic forms is observed during substitutive treatment., Case Report: A 13 year-old girl with Turner syndrome was examined for pubertal delay. Ultrasonography failed to see both ovaries and endocrine investigations showed a type P1 response (LH-RH test using immunological method). Control of hormonal levels by a polyclonal immunoenzymatic method confirmed primary hypogonadism., Conclusions: Radioimmunological methods using monoclonal antibodies can underevaluate FSH and LH levels under circumstances in which the distribution of isoforms may vary. Discrepancy must lead to the measure of gonadotrophins using polyclonal immunoenzymatic methods.

In vitro bioassay (BIO) is a very specific and sensitive method for determining levels of luteinizing hormone (LH). It provides a means of evaluating the values obtained with routine radioimmunoassays (RIA). Serum levels with bioassay are higher than those obtained with radioimmunoassay. The LH BIO/LH RIA ratio measures the difference between the two methods and gives a means of evaluating the quality of the LH secreted. The LH BIO/LH RIA ratio is significantly higher at the summit than at the nadir of the LH serum pulses. This ratio also increases after administration of GnRH. The differences in the quality of the LH can be explained by micro-heterogenicity. Immunofluorometric assay of LH (LH FIA) is much more sensitive than either the LH BIO or the LH RIA assays. Unlike the LH BIO/LH RIA ratio, the LH BIO/LH FIA ratio remains unchanged during LH pulses and after administration of GnRH. This difference can be explained by the lack of sensitivity but also by the lack of specificity of the LH RIA. LH RIA is not reliable when the serum levels of LH are low. However, RIA is valid when the serum levels of LH are increased as occurs in polycystic ovary syndromes.

The glycoprotein hormones are a family of four proteins: LH, FSH, TSH and CG. These molecules are glycosylated dimers, sharing a common alpha-subunit and differing by their beta-subunit which confers to the hormone its immunological and biological specificity. The biological function of these hormones is mediated through the recognition of specific receptors at the target organ. Although still controversial, it appears that both subunits of the hormone are required to bind to the receptor and induce cAMP release. Furthermore, these hormones exhibit natural variability in their bioactivity and the molecular basis of this process are poorly understood at the moment. Recent data relative to the mapping of glycoprotein hormones, were obtained by site-directed mutagenesis as well as by the use of synthetic peptides. These two approaches allowed to elucidate several linear peptide sequences involved in the biologically active conformation and immunoreactivity of these molecules. Furthermore, these hormones exist in different molecular forms with a variable biological activity and immunological ratio, and this polymorphism is probably due to the glycan moities. The presence of these glycans are necessary for full expression of their biological activity as well as immunoreactivity, and both the biosynthesis and the secretion of these various glycoforms are probably under physiological regulation. We therefore propose that glycosylation may alter the expression of several domains at the surface of the hormone to modulate its plasmatic clearance as well as the action of each individual glycoform at the receptor and this will ultimately control its biological function.

Plasmatic estradiol (E2), progesterone (P) and LH were measured during the follicular phase of 343 cycles induced for in vitro fertilization (IVF) using a LHRH agonist in a "long protocol" (Group I) and 76 cycles in a "short protocol" (Group II). Moreover measurements in the plasma and follicular fluid (FF) of E2, P, LH, Delta-4-androstenedione (A), Testosterone (T) and prolactin (PRL) were performed on the day of oocyte retrieval (DO) in 46 women of the group I (111 FF) and 27 of the group II (67 FF). In the group I, plasma LH always remains below 3 mUl/ml, whatever the type of agonist (Buserelin or DTRP6-LHRH) and the type of stimulation (HMG or FSH) are used. On the other hand in the group II, mean plasma LH and P levels from D-5 to D-2 and those of FF LH, T and A on DO are significantly higher than in the group I. These changes are associated with a significant decrease of retrieved oocytes (5.8 versus 7.8 p less than 0.0001), pregnancy rate (15% versus 30%, p less than 0.01) and ongoing pregnancy rate (10% versus 22%, per oocyte retrieval, p less than 0.01). They suggest that the pituitary desensitization could be unsatisfactory with the short protocol use of agonist.