Changes in the Metabolic Clearance Rate of Progesterone in the Guinea-Pig

Abstract

The metabolic clearance rate (MCR) of progesterone was measured by continuous infusion of the tritium-labelled steroid in guinea-pigs under light sodium pentobarbitone anaesthesia. In normal animals during the oestrous cycle, the MCR was 112\m=.\8 \ m=+-\ 7\m=.\0 (S.E.) 1 plasma/day/kg. In pregnant animals there was a sharp decrease in MCR between days 15 and 20, to 8\ m=. \ 3\ m=+-\ 0\ m=. \ 81/ day/kg. This low clearance rate was observed throughout the remainder of gestation. After parturition MCR returned slowly to non-pregnant levels, reaching 85 1/day/kg by day 12 post partum.The decrease in metabolic clearance rate occurred at the same time as the increase in plasma concentration of progesterone. This may be related to an increase in binding proteins with a high affinity for progesterone. The stimulus for the decrease in MCR in pregnancy is obscure but appears to depend on the presence of a viable conceptus. In the non-pregnant guineapig the MCR is not reduced by exogenous oestrogen, hysterectomy or hypophysectomy.

Properties of proteins binding plasma progesterone in pregnant Cape porcupines (Hystrix africaeaustralis)

“…4c) implies that only a small fraction of the total progesterone concentration would be free. This is supported by observations that approximately 2% of the total progesterone concentration is present in the free form and would be in agreement with the presumed function of PPBP (Illingworth et al, 1970;Heap & Illingworth, 1974). Since CBG also occurs in the plasma of pregnant Cape porcupines it appears that PPBP in Old and New World hystricomorph rodents are very similar in composition.…”

Effects of Oestrogen, Administered Early or Late in the Oestrous Cycle, Upon the Survival and Regression of the Corpus Luteum of the Guinea-Pig

“…When examined after the infusion experiments, the ovaries of the three animals contained the large CL typical of oestrogen-treated animals. The metabolic clearance rate (144+3-3 1/day/kg) was at the high rate typical of the non-pregnant animal (112 + 7-0 1/day/kg ;Illingworth et al, 1970). The produc¬ tion rate of progesterone, calculated from the metabolic clearance rate and plasma concentration, was almost 0-6 mg/day/kg.…”

“…Absorption from this amount of hormone is sufficient to main¬ tain the CL. The metabolic clearance rate was measured 10 or 11 days later, using the continuous infusion technique previously described in detail (Illing¬ worth, Heap & Perry, 1970).…”

Hormones of reproduction in farm animals

“…By definition a profile refers to an observation 'as seen from one side' and the determination of the concentration of hormone in blood gives a static rather than dynamic view of hormone secretion. An example of this difference is to be found in a laboratory animal, the guinea pig, in which the plasma progesterone concentration increases about 100-fold in pregnancy as a result of a 90 per cent decrease in the clearance rate of the hormone and only about a 3-fold rise in its production rate (illingworth, Heap and Perry, 1970). In this instance the hormone concentration in blood gives a misleading indication of the actual change in hormone production, ) during and after the infusion of ^H progesterone (Paterson, Bedford, Harrison and Heap, 1976).…”