Plasma clearance in the rat of the LH bioactivity of two human LH standards of differing molecular composition

Abstract

The LH biological potency of the International Reference Preparation (IRP) of Human Pituitary LH for Immunoassay (IRP 68/40) relative to that of the 2nd IRP of Human Pituitary FSH and LH for Bioassay (IRP 78/549) is markedly greater when estimated by in-vitro interstitial cell testosterone production (TICT) bioassay than by in-vivo bioassay, and by the 4-h ovarian ascorbate depletion (OAAD) assay than by the 4-day seminal vesicle weight gain assay. Other preparations of human LH which, like IRP 68/40, were highly purified, showed a similar spectrum of bioactivity in these assay systems and also contained a higher proportion of more basic LH isoforms than are found in crude pituitary extracts such as IRP 78/549. In an attempt to explain these differences, a comparison was made of the plasma survival in rats of the LH bioactivity (by TICT assay) of these two preparations. Contrary to expectation, their relative plasma clearance rates over a 4-h period did not account for their differing bioactivities. The plasma half-life of the LH bioactivity (with 95% confidence limits) was estimated to be 42.4 (35.3-49.5) min for IRP 68/40 and 41.3 (31.5-51.0) min for IRP 78/549. Furthermore the time-course of action in vivo of IRP 78/549 did not appear to be more prolonged than that of IRP 68/40. Thus their plasma testosterone responses during the course of these 4-h plasma clearance studies were similar, and estimates of the LH potency of IRP 68/40 relative to that of IRP 78/549 were no greater by 2-h than by 4-h OAAD assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Regulation of Luteinizing Hormone and Follicle-Stimulating Hormone in Male Siberian Hamsters by Exposure to Females and Photoperiod

“…The half-life of LH is 42 min (34). Three criteria were used to classify a male as having released gonadotropins in response to the presentation of a female.…”

Definition and Measurement of Follicle Stimulating Hormone

“…In vivo bioassays. Furthermore, while differences in in vitro bioactivity were not found to be reflected by differences in clearance of in vivo bioactivity (228), in vivo biological activity of LH was found by others (42) to reflect in vitro biological activity rather than clearance. Those isoforms of FSH that are relatively low in sialic acid content, and are hence relatively basic in nature, have a relatively low potency in in vivo bioassays (140) due presumably to their rapid clearance from the circulation.…”

New insights into the evolution of chorionic gonadotrophin

“…In addition, the CTP of CGB prolongs the β-subunit peptide and enables extensive glycosylation of four novel O-glycoslation sites at Ser121, Ser 127, Ser 132 and Ser 138 (Birken and Canfield 1977;Keutmann and Williams 1977). CTP glycosylation leads to a prolonged half-life of 5-6 hours for LH holohormone to 36 kDa for CG holohormone (Wehmann and Nisula 1981;Storring et al 1988;Haavisto et al 1995;le Cotonnec et al 1998a;le Cotonnec et al 1998b;le Cotonnec et al 1998c). The glycosylated CTP also results in an altered route of hormone secretion: LH is secreted baso-laterally from gonadotrophic storage granules after GnRH-stimulation, whereas CG is released constantly and apically by trophoblasts towards the maternal blood circulation system (Table 2) (Childs et al 1983;Handwerger et al 1987;Lloyd and Childs 1988;Currie and McNeilly 1995;Jablonka-Shariff et al 2002).…”