Progesterone-Binding Globulin and Testosterone-Binding Activity in Guinea Pig Serum During Pregnancy: Relationship to Progesterone and Oestrogens

Abstract

Progesterone levels in serum have been determined throughout pregnancy in guinea-pigs by a competitive protein-binding technique, using pregnant guinea pig plasma protein as binding agent. The concentrations of this protein (progesterone-binding globulin, PBG) as well as the testosteronebinding activity (TBA) have been quantitated by means of equilibrium dialysis. In order to correlate these parameters to the endogenous oestrogen production, the urinary oestrogen excretion was recorded. The concentration of progesterone, PBG and TBA showed a sharp rise on days 14\p=n-\18 of gestation, reaching a maximal level on days 30\p=n-\44.The progesterone level thereafter declined significantly towards parturition, followed by a sharp drop post partum. PBG and TBA followed a similar course, the decline towards parturition, however, being non significant. Neither progesterone, PBG nor TBA were significantly correlated to the urinary oestrogen excretion.The concentration of PGB was remarkably high, amounting to 1\ p=n-\ 2 \ m=x\10-5 m during most of the guinea pig pregnancy. This binding capacity generally exceeded the endogenous progesterone concentration by a factor of 20, as calculated on a molar basis. A mean of 64 % of the binding sites was available for testosterone binding, corresponding to a free binding capacity of 400 \g=m\g testosterone per 100 ml.During pregnancy, the progesterone-and testosterone-binding capacities of guinea pig plasma are reported to be well above the levels found in non pregnant animals (Diamond

Sex Steroids in Plasma and Reproductive Tissues of the Female Guinea Pig

“…It decreased by @‘¿ 50% at term. This pattern and the values for progesterone in the present study are in agreement with the data published previously (Heap and Deanesly, 1966;Challis et al, 1971;Croix and Franchimont, 1975;Lea et al, 1976). Plasma progesterone levels in the guinea pig at term are similar to those in man (Table 2).…”

Free and bound androgens in the female guinea pig during gestation and after parturition and in the offsprings during the perinatal period

“…It is known that a similaritv exists between the evolution of progesterone and testosterone in maternal plasma (Lea et al 1976); thereby, the androgens in general could be simple catabolites of placental progesterone. Concerning the high level of total DHT as opposed to that of total testosterone, this could be explained by the affinity of PBG which is 3 times greater for DHT than testosterone in spite of the reduced activity of the 5a-reductase in the plasma of the pregnant guinea pig (Tarn 1977 Lea & Stöa (1972), Lea (1973b), and Milgrom et al (1973) concerning the interaction of both DHT and T with PBG in the pregnant guinea pig.…”

Binding of 5α-dihydroprogesterone to proteins in human pregnancy serum

“…No data are available for the MCR in the human but experiments in the rabbit ) has shown that DHP clearance is actually twice that of progesterone. Only in the pregnant guinea pig and, possibly, other pregnant hystricomorphs, does the MCR of progesterone and DHP appear to be controlled by a high affinity binding protein (Illingworth et al 1970;Lea 1973b;Lea et al 1976). …”

“…It seems unlikely that these levels should be the result of a high peri¬ pheral 5a-reduction of progesterone since, in the human, progesterone metabolism has been shown to proceed mainly through the formation of 5ß-reduced steroids (Chang et al 1960;Davis et al 1960). High levels of DHP could also be explained by a low clearance rate caused by binding to high affinity binding proteins as has been shown to occur in the pregnant guinea pig (Illingworth et al 1970;Lea 1973b;Lea et al 1976). The aim of the present investigation is to examine the latter hypo¬ thesis by identification and comparison of serum proteins involved in the binding of DHP and progesterone.…”