OBJECTIVE
The purpose of this study was to estimate pharmacokinetic parameters and to evaluate placental transport of 17-hydroxyprogesterone caproate (17-OHPC) in singleton gestation.
STUDY DESIGN
Sixty-one women who received weekly injections of 17-OHPC underwent 2 pharmacokinetic studies at 20 + 0 to 24 + 6 weeks’ gestation (study 1) and 31 + 0 to 34 + 6 weeks’ gestation (study 2); daily blood samples were obtained between injections. In 18 women, blood samples were obtained over a 28-day period beyond the last injection (extended study). Maternal and/or cord blood were obtained at delivery.
RESULTS
The half-life (median ± SD) of 17-OHPC was 16.2 ± 6 days. Concentrations of 17-OHPC were higher during study 2 than during study 1. Body mass index affected maternal 17-OHPC concentrations. Cord:maternal 17-OHPC concentration ratios averaged 0.2; 17-OHPC was detectible in cord plasma 44 days after the last maternal injection.
CONCLUSION
The apparent half-life of 17-OHPC is long, and pharmacokinetic parameters vary widely between subjects and are affected by maternal body mass index. The drug crosses the placental barrier.
RT-PCR to be transcribed, albeit with different ef®ciency. The mRNA levels for each gene were determined as: b5 > b3 = b8 > b7 > b1,b2. 12 It is possible that the presence of tandemly arranged genes with identical coding sequences may have a role in the high expression of hCG in early pregnancy.
STRUCTURE OF HCGThe glycoprotein hormone family are believed to share similar structural features although to date only the structure of hCG has been elucidated. Two groups independently resolved the x-ray crystallographic structure. One study used hydrogen uoride treated protein 13 and the other used recombinant selenomethionyl protein. 14 Both groups revealed almost identical structures, with residues 2 ± 111 in the b and 5 ± 89 in the a subunits traced. The failure to identify the C-terminal extension of hCGb implies that it is a poorly ordered structure. The a-and b-subunits each have remarkably similar folds. They are elongated with two adjacent loops at one end and a single long loop projecting in the opposite direction. When the heterodimer is formed the single loop of one subunit lies adjacent to the double loops of the other subunit. The b subunit of hCG has six disul®de bonds and the alpha subunit has ®ve disul®de bonds. The crystal structure revealed that the previously de®ned disul®de bonds could not all be made. 15,16 These disul®de bonds appear to play an integral role in maintaining the heterodimeric structure. At the core of the hCGa and b subunits is a cystine knot motif from which the loops project out. This motif, also found in neural growth factor, platelet derived growth factor and tumour growth factor b, is formed by two adjacent parallel strands joined by two disulphide bonds forming a ring, through which another disulphide bond is looped joining a second pair of strands. The subunit similarity is at its highest in the area of the cystine knot. With the elongated structure of hCG there is a high ratio of protein surface to hydrophobic core and the subunits associate to a large extent over the whole surface. The majority of the structural motifs in the loops are b-sheet and b-turns. In the long loop of the alpha chain there are, however, two turns of an a-helix. The loop from Cys 90 to Cys 110 in the b subunit is wrapped over and through the long loop of the a-subunit. This`seat belt' is held in place by the cystine bond b26 ± 110, which is the last disulphide to form in the folding pathway of hCG. 17,18 These structural features together with the observation that the individual subunits are inactive, have implied that the quaternary structure provided by the assembly of the alpha and beta subunits is important for hCG function. However, recent work with genetically fused alpha and beta subunits which are mutated in assembly critical residues, or in cysteine pairs forming disul®de bonds have shown that the heterodimeric con®guration is more important for assembly and secretion than for biological activity. 19,20,21 HCG is heavily glycosylated with the carbohydrate content accounting for 30% of the ...
Case I.\p=m-\OnDecember 5th, 1888, I performed laparotomy for what was supposed to be a pelvic abscess in a woman 25 years old who had been married three years and had never borne children.
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