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1.
J Endocrinol Invest ; 10(3): 283-90, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3624801

ABSTRACT

Estrogen glucuronides are selectively cleared by the kidney as compared to estrogen sulfates. The selective trafficking of circulating serum estrogen conjugates to kidney and urine may arise from differential transport properties of the various estrogen conjugates in the renal microcirculation. In the present study, the effects of glomerular and peritubular permeability barriers, and plasma protein binding on the influx of unconjugated and conjugated estrogens into rat kidney were studied. Experiments were carried out utilizing an in vivo double isotope, single injection, timed tissue sampling technique. The extractions of these steroids by the renal cortex were examined utilizing inulin as the reference substance, as it is freely permeable through the glomerular and tubular capillary permeability barriers, but not extracted by tubular epithelial cells. The method was validated by studying the extraction of para-amino hippuric acid (PAH) before and after probenecid treatment. In the absence of plasma proteins, all the estrogens and estrogen conjugates readily diffused through both the glomerular and peritubular capillary permeability barriers and were extracted by tubular epithelia. The addition of 4% albumin to the injection solution led to significant inhibitions of extraction of estradiol (E2) and estrone sulphate (E1-S) only. The extraction of E1-S was reduced to a value less than that of inulin; the extraction of E2 was less than that of control value but significantly more than that of inulin. The addition to the injection solution of human pregnancy sera containing sex hormone binding globulin and albumin was associated with a reduction in the extraction of all estrogens and estrogen conjugates except estriol and E1-S to values approximating that of inulin.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Proteins/metabolism , Estrogens/metabolism , Kidney Cortex/metabolism , Animals , Female , Inulin/metabolism , Protein Binding , Rats , Rats, Inbred Strains
2.
J Clin Endocrinol Metab ; 59(6): 1128-32, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6092408

ABSTRACT

The role of capillary membrane permeability and the effect of plasma protein binding on the influx of unconjugated and conjugated estrogens into a target organ, the uterus, and a metabolic organ, the liver, were studied in anesthetized rats. In the absence of plasma proteins, estrone (E1) and estradiol (E2) were freely diffusible through the uterine capillaries, but influx was significantly reduced for estriol (E3) and estetrol. In the uterus, the influx of the conjugated estrogens was markedly restricted and approximated the influx of dextran, a vascular space marker. The polarity of the compound (based on the number of hydrogen bond-forming functional groups and the presence of charged groups) appeared to predict uterine endothelial membrane permeability better than the octanol/Ringer's partition coefficient. In contrast to the selective permeability properties of the uterine endothelial barrier, the limiting membrane lining the hepatic microcirculation, the hepatocyte cell membrane, was highly permeable to all unconjugated and conjugated estrogens. The addition of 4% albumin to the injection solution led to a significant inhibition of uterine influx of E2, but not E1 or E3. In the liver, only the influx of E1 sulfate was slightly diminished by 4% albumin. In all cases, the influx of estrogens greatly exceeded the rate that would be expected if only the fraction that was free (dialyzable) in vitro was diffusible in vivo. Human sera containing sex hormone-binding globulin and albumin caused inhibition of influx of E1 and E2 through the uterine capillary barriers, whereas in the liver, the influx of E2 sulfate, and E3 glucuronide were diminished. The results are compatible with a difference in permeability of the microvasculature of the two organs and a differential availability of protein-bound estrogen for influx into liver and uterus. With the exception of E1, which is nearly completely diffusible into both organs, the influx of estrogens and estrogen conjugates into liver is greatly amplified compared to that into a peripheral organ such as the uterus.


Subject(s)
Estrogens/metabolism , Liver/metabolism , Uterus/metabolism , Animals , Biological Availability , Blood Proteins/metabolism , Estrogens, Conjugated (USP)/metabolism , Female , Liver/blood supply , Permeability , Protein Binding , Rats , Rats, Inbred Strains , Serum Albumin/metabolism , Sex Hormone-Binding Globulin/metabolism , Uterus/blood supply
3.
J Clin Endocrinol Metab ; 58(3): 578-81, 1984 Mar.
Article in English | MEDLINE | ID: mdl-6420445

ABSTRACT

Hot flashes have a close temporal relationship with the initiation of LH pulses, suggesting that factors stimulating gonadotropin release are involved in the mechanism of this disturbance. It has been reported that the opiate antagonist naloxone acutely blocked subjective hot flashes, a seemingly paradoxical effect, since the use of this agent in premenopausal women increases the magnitude and frequency of LH pulses. We, therefore, studied the effects of naloxone in 16 postmenopausal women with frequent hot flashes using continuous recordings of finger temperature and skin resistance as objective indices of flushing and perspiration, respectively. After baseline recordings, the subjects were randomized into equal groups, and the recordings were repeated during 8-h infusion of either saline or naloxone (22 micrograms/min). Serum gonadotropin levels were measured at 15-min intervals before and during the last 4 h of the infusion. Naloxone did not change the rate of objectively measured hot flashes, mean serum LH or FSH levels, or the frequencies or amplitudes of gonadotropin pulses. These data suggest that there is a very low input of endogenous opiates on gonadotropin secretion in postmenopausal women and that opioid peptides do not play a role in the initiation of the postmenopausal hot flash.


Subject(s)
Climacteric/drug effects , Follicle Stimulating Hormone/blood , Luteinizing Hormone/blood , Menopause/drug effects , Naloxone/pharmacology , Aged , Body Temperature/drug effects , Female , Galvanic Skin Response/drug effects , Humans , Middle Aged
4.
Neuroendocrinology ; 36(2): 102-4, 1983 Feb.
Article in English | MEDLINE | ID: mdl-6339975

ABSTRACT

To assess the permeability of the blood-brain barrier (BBB) to exogenously administered gondatrophin-releasing hormone (GnRH), a study was performed in male-rats using the double isotope, intracarotid, single injection technique of Oldendorf. The mean (+/- SEM) brain uptake indices (BUI) of 3H-GnRH in comparison to a freely diffusible reference compound, 14C-butanol, were 1.1 +/- 0.2, 3.5 +/- 0.7 and 3.0 +/- 0.6 when the injection vehicles were Ringer's lactate, rat serum and human serum, respectively. The BUI of 3H-GnRH was similar to that of 3H-inulin, a nondiffusible compound. With different concentrations, the BUI of 3H-GnRH did not change significantly. These data indicate that the BBB of the male rat is impermeable to exogenously administered GnRH.


Subject(s)
Blood-Brain Barrier , Capillary Permeability , Rats/physiology , Animals , Biological Transport , Brain/metabolism , Male , Pituitary Hormone-Releasing Hormones/metabolism , Rats, Inbred Strains
5.
Z Geburtshilfe Perinatol ; 183(6): 448-52, 1979 Dec.
Article in English | MEDLINE | ID: mdl-547544

ABSTRACT

A randomized study to evaluate the effect of natural estrogens on the unripe uterine term cervix was conducted. One hundred and five term gravidas were studied, of whom 70 were treated with 180 mg 17 beta-estradiol or 250 mg estriol (treated women) and 35 were treated with gel only (control group). In all subjects the distented Foley catheter used for the instillation was left in situ. Twelve hours after the instillation there was no apparent difference in mean cervical progress between treated women and controls and the rather unexpected degree of cervical ripening is atributed to the intra-uterine balloon catheter. The procedure could not be shown to have any untoward effect on the mother or the fetus.


Subject(s)
Cervix Uteri/drug effects , Estrogens/therapeutic use , Uterine Cervical Incompetence/drug therapy , Acid-Base Equilibrium , Administration, Topical , Adult , Estradiol/therapeutic use , Estriol/therapeutic use , Estrogens/administration & dosage , Female , Humans , Lactates/blood , Pregnancy , Pyruvates/blood
7.
Z Geburtshilfe Perinatol ; 182(5): 352-7, 1978 Oct.
Article in English | MEDLINE | ID: mdl-735273

ABSTRACT

Pre-induction ripening of the unfavorable cervix was attempted in 104 normal term gravidas by means of a single extra-amniotic instillation of a viscous gel containing 0.5 mg prostaglandin E2. The procedure was highly successful and no adverse effect on mother or fetus was observed.


Subject(s)
Cervix Uteri/drug effects , Labor, Induced , Prostaglandins E/administration & dosage , Adolescent , Adult , Amnion , Apgar Score , Delivery, Obstetric/methods , Female , Fetal Monitoring , Gels , Humans , Infant, Newborn , Parity , Pregnancy , Prostaglandins E/pharmacology
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