Retention Of Progesterone Research Articles

Retention of progesterone by four carbonaceous materials: Study of the adsorption equilibrium

The adsorption process of a natural steroid hormone (progesterone) by four carbonaceous adsorbents has been studied. The corresponding equilibrium isotherms have been analyzed according to a previously proposed model which establishes a kinetic law satisfactorily fitting the C versus t isotherms. The obtained equilibrium isotherms consist of three segments, which have been separately discussed. Different equations corresponding to each of the referred segments have been proposed, the experimental data being fitted to such equations. From the values of the kinetic equilibrium constant corresponding to the second—and more significant—of the above mentioned segments, values of standard average adsorption enthalpy (Δ H°) and entropy (Δ S°) have been calculated. Finally, information related to variations of differential adsorption enthalpy (Δ H) and entropy (Δ S) with the surface coverage fraction ( θ) was obtained by using the corresponding Clausius-Clapeyron equations.

Retention of Progesterone by an Activated Carbon: Study of the Adsorption Kinetics

The process by which progesterone in an ethanol solution is retained by Merck granular activated carbon involves a reversible mechanism that conforms to a kinetic equation of unity partial order in both the progesterone concentration in solution, the coverage fraction (θ) of the adsorbing surface and (1−θ). Over the temperature range 10–40°C, the specific adsorption rate varies from 5.8·10−5 to 1.3·10−4 s−1. The thermodynamic activation functions for the process are ΔH*=41.6 kJ/mol and ΔS*=−0.20 kJ/K· mol. The rate of the adsorption-desorption process is primarily determined by diffusion of progesterone molecules in the pores of the sorbent.

Retention of progesterone by four carbonaceous materials: study of the adsorption kinetics

The process by which progesterone in an ethanol solution is retained by four carbonaceous materials involves a reversible mechanism that conforms to a kinetic equation of unity partial order in both the progesterone concentration in solution, the coverage fraction (u ) of the adsorbing surface and (1� /u ). Over the temperature range 10 � /40 8C, the specific rate constant varies from 5.29 � /10 � 4 to 44.85 � /10 � 4 s � 1 . The formation of the activated species involved in the adsorption process is an endothermal, exoentropic step. The rate of the adsorption � /desorption process is primarily determined by diffusion of progesterone molecules in the pores of the sorbent. # 2003 Elsevier B.V. All rights reserved.

A progesterone binding component in porcine ovarian follicular fluid.

Steroid hormone concentrations (progesterone, oestrone, oestradiol-17 beta) in porcine follicular fluids were measured by radioimmunoassay. In confirmation of several previous studies, as follicular maturation proceeded, the concentrations of all three steroids increased, although the relative amounts of the oestrogens decreased compared to progesterone. Analysis of fluids for steroid-binding components was undertaken using ion-exchange chromatography, gel filtration and steroid-binding assays. Evidence is presented in support of a labile binding component which exhibits high affinity and low capacity for progesterone and little or no affinity for oestadiol. Our findings are discussed in relationship to the known retention of progesterone within preovulatory follicles and to previous reports of steroid-binding components in follicular fluids.

The metabolic clearance rate and uterine metabolism and retention of progesterone and 20alpha-hydroxypregn-4-en-3-one during the secretion of uteroglobin in ovariectomized, steroid-treated rabbits.

The metabolic clearance rate (MCR) and in vivo uterine metabolism and retention of progesterone (P) and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) during the uterine synthesis of uteroglobin in the rabbit have been studied. Oophorectomized rabbits with the uteri ligated received daily im injections of oil vehicle (C), 2 mg P/kg BW, or 2 microgram estradiol/kg BW. The MCR of [14C]P and [3H]20 alpha-OHP did not differ among treatment groups and was 260 +/- 30 and 270 +/- 33(SE) liters/day, respectively. Although the uterine tissue to arterial blood ratio of [14C]P differed between groups (E greater than C greater than P), the tissue to blood ratio of 20 alpha-OHP was the same for the three groups and was about 1. The uterine extraction of P was 32 +/- 6.2(SE)% and was the same for the three treatment groups. The uterine extraction of 20 alpha-OHP was significantly increased by estrogen treatment [33.4 +/- 6.0(SE)%] compared to the control [14.8 +/- 3.3(SE%)] or P[16.9 +/- 4.5(SE)%] groups. These studies indicate that the ability of exogenous 20alpha-OHP to stimulate uteroglobin secretion is probably mediated by its peripheral conversion to P. These studies also indicate the value of continuous infusion of radioactive steroids to evaluate tissue retention and metabolism in vivo.

Progesterone Retention by Rat Uterus I: Pharmacokinetics after Uterine Intraluminal Instillation

Tritium-labeled progesterone was administered to mature female rats in the proestrous stage by three different routes, gastric intubation, subcutaneous injection, and uterine intraluminal instillation, to study the kinetics involved in the uptake and retention of radioactivity by the uterus and various other tissues. Progesterone was retained at a much higher level and for a more prolonged period in the rat uterus after uterine intraluminal instillation. Progesterone bioavailability to the uterus was 45 times higher by uterine intraluminal instillation than by either gastric intubation or subcutaneous injection. Progesterone absorption by the rat endometrium was extremely fast. The observed biphasic decrease of radioactivity from the uterine tissue was explained adequately by a pharmacokinetic model in which progesterone is assumed to be present in two compartments within the uterine tissue. The pharmacokinetic parameters showed that the progesterone biological half-life in the uterine tissue during the a-phase was about 6.5min while that in the β-phase was about 230min.

The metabolic clearance rate, the brain extraction and distribution and the uterine extraction and retention of progesterone and R 5020 in estrogen-treated ovariectomized rabbits.

The metabolic clearance rate (MCR), uterine extraction, uterine retention and brain distribution of the synthetic progestin R 5020 and progesterone were studied in estrogen-treated ovariectomized rabbits. The MCR of R 5020 was 163+/-15 (SE) 1/day and was lower than that of progesterone. The uterine extraction of R 5020 (51.4+/-3.9 (SE)%) was greater than that of progesterone (33.7+/-7.7%) as was the uterine tissue:arterial blood ratio (28.1+/-4 vs. 7.3). The brain and pituitary retention and distribution of R 5020 and progesterone were the same and provided no evidence for a selective accumulation of a progestin in the pituitary or hypothalamus.

Progesterone may act at hypothalamus and pituitary by way of enhancement of oestrogen retention

PROGESTERONE injection given 24 h or more before ovulation inhibits the ovulatory cycle1–5. There is evidence that progesterone can act directly on the hypothalamus6–9 to block ovulation and on the pituitary to reduce pituitary sensitivity to luteinising releasing hormone10,11. Steroid-sensitive target tissues including hypothalamus12,13 and pituitary14–16 contain a specific oestrogen retention mechanism of limited capacity. Oestrogen-regulated events can be demonstrated only in the presence of a functional retention (receptor) system for oestrogen. In contrast, no specific progesterone retention system has yet been demonstrated for hypothalamus or pituitary. Does progesterone interact with these target tissues in a novel manner? This seems unlikely since other steroids which have been studied—for example, adrenal corticoids17 and androgens18—have been found to bind to specific receptors in their target tissues. We therefore tested an alternate possibility that progesterone action on hypothalamus and pituitary might result in modification of the oestrogen receptor system. We tested 3H-oestradiol retention by hypothalamus and pituitary after in vivo treatment with progesterone (subcutaneous pellet; release rate=1.5–3 mg d−1) of various durations from hours to days. In vitro 3H-oestradiol-specific retention by oestradiol–receptor complexes transferred to the nuclear fraction of these tissues was also compared for animals receiving previous in vivo progesterone treatment compared with ovariectomised animals not receiving progesterone treatment.

The head extractions, brain and pituitary uptake and metabolism of progesterone and 5α-dihydroprogesterone in anesthetized, female rabbits

Three days after ovariectomy adult female rabbits were injected intramuscularly with either 2 μg estradiol/kg b.w., 0.5 mg progesterone/kg b.w., 2 μg estradiol plus 0.5 mg progesterone/kg b.w., or oil vehicle daily for 5 days. On the sixth day the animals were anesthetized and given a continuous infusion of [ 14C]progesterone and [ 3H]5α-pregnane-3,20-dione (5α-DHP) for 4 h via the femoral vein. Head extractions, calculated from the difference in blood concentrations of radioactive steroids between the femoral artery and jugular vein, were in the range of 60–75% for both progesterone and 5α-DHP and were unaffected by the hormone treatments. Nine brain areas and the pituitary were analyzed for [ 14C]progesterone, [ 3H]5α-DHP and [ 14C]5α-DHP. Generally, the brain and pituitary retention and distribution of [ 14C]progesterone and [ 3H]5α-DHP and the brain and pituitary metabolism of [ 14C]progesterone were unaffected by hormone treatments. In the cerebellum, progesterone treatment increased [ 14C]progesterone retention as compared to oil treatment. All tissues contained 2–7 times more [ 14C]progesterone than arterial blood concentrations. [ 3H]5α-DHP tissue: arterial blood concentrations ratios were much lower ranging from 0.9 to 1.78. [ 14C]progesterone and [ 3H]5α-DHP showed similar brain distribution with highest concentrations in the pons, pons reticulum and midbrain reticulum. All tissues converted progesterone to 5α-DHP, but only the cerebellum contained more [ 14C]5α-DHP than [ 14C]progesterone.

Uptake of 3H-progesterone by brain and pituitary of castrated male rats.

Gonadectomized male rats of Wistar strain were administered 3H-progesterone. Various brain tissues and anterior pituitary were analyzed for retention of radioactivity, using a liquid scintillation technique. Radioactivity, in all tissues, was highest at 20 min after steroid treatment, and thereafter dropped nearly in the same pattern as each other. Among the tissues examined median eminence and anterior pituitary retained more radioactivity for a longer period of time than did other tissues. The results suggest that there is long-term retention of progesterone in the median eminence and anterior pituitary of male rats.

Effects of oestrogen priming on the uptake, metabolism and biological activity of progestins in the mouse uterus.

SUMMARY The effects of single subcutaneous injections of progesterone on uterine stromal and uterine epithelial mitosis and morphology varied non-linearly during the 6 days after oestrogen priming. Retention of locally applied progesterone was significantly less and recovery of its metabolites greater on day 1 after oestrogen priming than on day 6. Recovery of metabolites of two potent synthetic progestins, megestrol acetate and medroxyprogesterone acetate, was negligible after injection on either day. Retention of these progestins was the same whether given on day 1 or day 6, and was similar to the retention of progesterone when injected on day 6.

Neural uptake of [1, 2- 3H]progesterone in ovariectomized rats, guinea pigs and hamsters: Correlation with species differences in behavioral responsiveness

The time-course of neural uptake, metabolism, and release of [1, 2- 3H]progesterone was studied in ovariectomized, estrogen-primed rats, guinea pigs, and hamsters in an attempt to correlate species differences in these measures with previously noted differences in behavioral responses to the hormone. The principal findings were: (1) Rat and guinea pig brain took up progesterone in the same pattern; highest uptake was found in the midbrain followed by the hypothalamus, cerebral cortex, and hippocampus. Midbrain uptake was highest in hamster brain, but no consistent uptake pattern was found in the other brain tissues. (2) Guinea pig brain seemed to have a higher affinity for progesterone (indicated by tissue/plasma concentration ratios) than hamster brain, which took up more hormone than rat brain. This pattern was especially striking in midbrain and hypothalamus, where intracerebral progesterone implants have been reported to affect sexual receptivity. (3) Guinea pig and hamster brain retained injected progesterone for a longer time than rat brain. (4) Rat and hamster brain metabolized progesterone more extensively than guinea pig brain. (5) It is suggested that the species differences in neural affinity for progesterone might be responsible for the differential sensitivity to the facilitatory actions of progesterone on estrous behavior. In addition, the prolonged retention of progesterone by guinea pig and hamster brain could be the basis for the post-estrous refractoriness to exogenous hormones found in these species.

Uptake and metabolism of (1,2-3H)progesterone injected intraluminally into the uteri of spayed mice.

SUMMARY [1,2-3H]Progesterone (5–50 pg) injected intraluminally into the uterus of spayed mice was retained only to a small extent; producing a 'half-life' of about 30 min compared with > 240 min for [6,7-3H]oestradiol-17β (50 pg). Retention of progesterone by the uterus was not significantly different from that by the plantaris muscle, a non-target tissue. Paper chromatography of extracts indicated that metabolism of [1,2-3H]progesterone occurred in both the uterus and the vagina within 5 min of local injection. There was more metabolism in the vagina and it was qualitatively different. No selective retention of progesterone or its metabolites occurred in either organ. The proportion of the radioactivity present as progesterone over 120 min after injection remained constant.

Neural receptor mechanisms for estrogens and progesterone and the regulation of ovulation and sex-related behavior in mammals

The roles of estrogen and progesterone for maintenance of the cyclicity characteristic of the mature, reproductively active female are examined in detail for two species, rats and hamsters. In both species, regulation of cycle length, the timing of the receptive period, and the length of the receptive period are shown to be under the control of progesterone. Thus progesterone is the most important of the sex steroids for maintenance of cyclicity. The locus of hormone action is examined and it is shown that estrogen exerts both its negative feedback effects in regulation of the pituitary-gonad axis and its priming effects for receptivity at the level of the hypothalamus. Progesterone blocks ovulation by an effect on the hypothalamus (hamster); however, no localized action could be demonstrated for progesterone synergism with estrogen for induction of receptivity. Hormone retention by target tissues was examined and shown to be sex specific. When estrogen priming was done at “physiological” levels, increased retention was noted for target tissues of the female, while suppression of retention occurred in the male. Progesterone was found to interact with the estrogen-primed system resulting in a suppression of estrogen retention in the female and a mirror-image effect in the male, that is increased retention. Progesterone retention has been demonstrated for the uterus only and the retention is estrogen dependent, increasing with increased amounts of estrogen priming.

The Physiology of Hormone Receptors

SYNOPSIS. Hormone retention by various target tissues has been demonstrated for a number of sex steroids. Retention of the steroid by the target tissue appears to be specific and saturation occurs at physiological levels of hormone. Thus, target tissues are said to possess specific receptors for the hormone. Only the estrogens have been extensively studied, and both a cytoplasmic and nuclear receptor have been described for various estrogen target tissues (uterus, pituitary, hypothalamus). The receptor concept has been utilized by a number of laboratoriesas a mechanism which might be helpful in understanding the relationship between estrogen effects, i.e., changes in physiology or behavior resulting from estrogen treatments. The basis for the estrogen receptor is reviewed along with the data which attempt to relate hormone retention to a physiological response. There is considerable evidence that hormone retention is a primary step in the tissue hormone interaction as in its absence the effects attributable to the presence of the hormone are not observed. Progesterone retention has also been demonstrated forsome target tissues, and an estrogen (priming) component is apparent for uterus and vagina. Todate there is no concrete evidence lor specific progesterone retention at the neural level.

Uptake of tritiated progesterone by the uterus of the ovariectomized guinea pig.

In vivo studies in castrate guinea pigs demonstrated longer retention of progesterone- 3H in uterus than in heart or diaphragm. Estrogen pretreatment for 2 days increased the progesterone-3H uptake 7-fold in uterus but not in the other organs. Analysis of the estrogenprimed uterus revealed that 88% of the total radioactivity was progesterone-3H 1 hr after injection. The uterine uptake of progesterone-H3 was blocked by progesterone but not by cortisol, estradiol or testosterone treatment, The distribution of tritium in blood, heart and diaphragm was not influenced by any of the 4 steroids. These in vivo observations suggest that progesterone binding to estrogen-primed uterus is specific and of limited capacity. (Endocrinology86: 1059,