Does 2-hydroxyestrone suppress prolactin in women?
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Adult↗
Biomedical subjects
D L Loriaux
Publications and source records attributed to D L Loriaux.
Daily rhythm of plasma melatonin in normal and precocious puberty.
A previous study of normal humans has shown a decrease in plasma melatonin at the onset of puberty, suggesting that melatonin may act to restrain pubertal onset. We have measured plasma melatonin throughout a 24-h period in normal and constitutionally short males at different pubertal stages and in patients with idiopathic true precocious puberty and familial male isosexual precocity. The 24-h profile of plasma melatonin was similar for the prepubertal, pubertal, and adult males studied, with all subjects having low levels (20-50 pg/ml) during the day and high levels (80-100 pg/ml) at night between 0100-0500 h. The 24-h profiles of the patients with isosexual precocity were similar to the profiles observed throughout normal puberty. These data do not support a role for melatonin in the initiation of normal or precocious puberty in man.
Adolescent↗
The squirrel monkey: receptor-mediated end-organ resistance to progesterone?
Fertile females of a New World primate species, the squirrel monkey (Saimiri sciureus), have plasma progesterone concentrations that vary between 57 and 510 ng/ml during the reproductive cycle and are 10- to 20-fold higher than those seen in cynomolgus monkeys (Macaca fascicularis) and other Old World primates, including man. The plasma progesterone level during pregnancy is high and varies between 140 and 490 ng/ml. Estradiol levels during the reproductive cycle and pregnancy are also higher than those of cynomolgus monkeys. After 2-day treatment of ovariectomized monkeys with estradiol in oil, the progesterone receptor content in the uterine cytosol of the squirrel monkey is one eighth that in similarly treated cynomolgus monkeys [60.4 +/- 6.5 fmol R5020 bound/mg protein vs. 496 +/- 55 (mean +/- SE); n = 8]. The receptor affinity for R5020 is the same in both species. Thus, the elevated plasma progesterone levels in squirrel monkeys appear to be a compensatory response to a receptor-mediated decrease in sensitivity to progesterone. The squirrel monkey may be a model for the study of the mechanism of action and regulation of secretion of progesterone.
Animals↗
The effects of corticotropin releasing factor on the anterior pituitary function of stalk-sectioned cynomolgus macaques: dose response of cortisol secretion.
The recent identification of ovine corticotropin releasing factor (CRF), a 41-amino acid peptide, provides a potential new approach to evaluate disorders of the hypothalamic-pituitary-adrenal axis. We report here the effects of this new factor in the pituitary stalk-sectioned cynomolgus macaque. Given as an intravenous bolus, CRF stimulated cortisol secretion with an ED50 between 0.1 and 1 microgram/kg body weight. The peak cortisol response occurred after 15--30 min at low doses (0.5--1 microgram/kg) and after 45--90 min at higher doses (2--40 microgram/kg). This factor also stimulated the release of growth hormone and prolactin, but had no effect on TSH or LH secretion.
Animals↗
Metabolic clearance rate and plasma half-life of radioiodinated corticotropin releasing factor in a primate.
Corticotropin releasing factor (CRF) has recently been identified, purified and shown to be a 41-amino acid polypeptide that stimulates secretion of beta-endorphin and ACTH. The metabolic clearance rates (MCR) of I125-CRF and I125-TyroCRF were measured in cynomologus monkeys using the pulse injection and the continuous infusion methods. Hunter-Bolton reagent was used for iodination of CRF and the chloramine-T method for Tyro-CRF. Gel chromatography was used to separate free iodine (and radioiodinated small fragments) from iodinated CRF in plasma samples. Disappearance of I125-CRF or I125-Tyro-CRF could be modeled with two components (bi-exponential). Plasma half-life of I125-CRF was 17.1 +/- 2.44 min (mean +/- SE, n=4) for the fast component and 198 +/- 5.3 min for the slow component. The MCR of I125-CRF using the pulse injection technique was 0.44 +/- 0.06 L/Kg/d, n=4 and the volume of distribution 213.5 +/- 12 ml, n=4, roughly equal to the plasma volume. Continuous infusion of I125-CRF and of I125-Tyro-CRF gave MCR's ranging between 2.23 -= 5.08 L/Kg/d, n=4. I125-ACTH MCR, measured for comparison using the same technique, was 5-10 fold higher. Thus, the plasma half-life of CRF is longer than for all other known hypothalamic peptides and its metabolic clearance rate relatively low and considerably less all other known hypothalamic peptides and its metabolic clearance rate relatively low and considerably less than that of ACTH. Strong binding of CRF to plasma proteins may be responsible for the small volume of distribution and lower MCR values for the pulse injection method.
Adrenocorticotropic Hormone↗
Serum adrenal androgens in hyperprolactinaemic women prior to, during, and after chronic treatment with bromocriptine.
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Adult↗
Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease.
The importance of late-onset congenital adrenal hyperplasia as a cause of hirsutism is controversial. Two of 35 women with a chief complaint of hirsutism met the criteria of 21-hydroxylase deficiency. In one, who presented with hirsutism, oligomenorrhea, obesity, infertility, and enlarged cystic ovaries, the initial diagnosis was polycystic ovarian syndrome. Family data showed that her disorder was autosomal recessive and linked to the histocompatibility leukocyte antigens (HLA), as in the classic form of congenital adrenal hyperplasia. Carriers were thus detectable by HLA typing. Thus late-onset congenital adrenal hyperplasia appears to be an allelic variant of congenital virilizing adrenal hyperplasia with a milder enzymatic defect. The diagnosis cannot be made clinically because the disease has the same presentation as idiopathic hirsutism or polycystic ovarian disease. Basal plasma 17-hydroxyprogesterone levels, unlike in classic congenital adrenal hyperplasia, can be normal, and an ACTH stimulation test or sequential measurements of plasma 17-hydroxyprogesterone throughout the day may be needed to show the abnormality. The incidence among hirsute women is estimated to be 6% to 12%, and the calculated gene frequency for the allele coding for attenuated expression of 21-hydroxylase deficiency is 0.015 to 0.057.
Adrenal Hyperplasia, Congenital↗
Late-onset 21-hydroxylase deficiency.
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Adrenocorticotropic Hormone↗
The catechol estrogens: physiologic studies.
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Animals↗
Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report.
The uncoupling of pituitary stimulation and response observed in adults during administration of the luteinizing hormone-releasing hormone analogue, D-Trp6-Pro9-NEt-LHRH (LHRHa) suggested that this drug might be useful in treating precocious puberty. We treated five girls with idiopathic precocious puberty (ages two to eight) for eight weeks with daily subcutaneous injections of LHRHa. The patients had Tanner II to IV pubertal development, advanced bone age, an estrogen effect on vaginal smear, measurable basal gonadotropin levels with pulsed nocturnal secretion, and a pubertal gonadotropin response to LHRH. Irregular vaginal bleeding was present in three patients. LHRHa significantly decreased basal (P less than 0.025) and LHRH-stimulated (P less than 0.01) gonadotropin levels as well as serum estradiol (P less than 0.05). The vaginal maturation-index score, which reflects the estrogen effect, fell by 25 per cent. Eight weeks after stopping treatment, all hormonal values and the vaginal maturation index had returned to pretreatment levels. These favorable short-term results will need further study before the benefits and risks of chronic treatment with LHRHa can be adequately assessed.
Child↗
Testicular volume during early infancy.
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Humans↗
Unilateral testicular enlargement resulting from inapparent 21-hydroxylase deficiency.
We report a case in which unilateral testicular enlargement was the only presenting sign in 21-hydroxylase deficiency of the "acquired" or adult onset type. Measurement of plasma 17-hydroxyprogesterone throughout 24 hours revealed marked elevations, mostly between 0400 and 0700 hours. However, this steroid increased more than 18-fold 30 minutes following adrenocorticotropic hormone administration, confirming the diagnosis. Glucocorticoid therapy corrected the testicular enlargement. Inapparent 21-hydroxylase deficiency is a medically treatable cause of testicular enlargement that can be diagnosed by measurement of plasma 17-hydroxyprogesterone during a 30-minute adrenocorticotropic hormone stimulation test.
Adrenal Hyperplasia, Congenital↗
Developmental changes in rabbit and dog adrenal function: a possible homologue of adrenarche in the dog.
Histologic, hormonal, and enzymatic studies were performed in the rabbit and dog to identify maturational changes similar to human adrenarche. Development of an adrenal reticular zone was observed in both the rabbit and dog, analogous to the change in the man. Plasma dehydroepiandrosterone (DHA) and androstenedione (delta 4-A) increased significantly in postpubertal compared to prepubertal male rabbits and dogs, but the increases were much smaller than those reported in man. Orchiectomy reduced plasma DHA and delta 4-A of adult rabbit and dog to near undetectable levels, suggesting a primarily testicular origin. The activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase in the orchiectomized rabbit and dog were subsequently measured to explain this apparent low adrenal contribution to DHA and delta 4-A. Adrenal 17-hydroxylase activity in the rabbit ad 17,20-desmolase activity in both the rabbit and dog were significantly lower than in an adrenal androgen-secreting primate (cynomolgus macaque). Adrenal 17-hydroxylase activity in the dog, measured 1 wk after castration, doubled after sexual maturation (P less than 0.001). This change was paralleled by a significant rise in basal and ACTH-stimulated plasma 17-hydroxyprogesterone in the intact dog (P less than 0.05). Because adrenal 17-hydroxylase activity has been shown to increase during adrenarche in man, this change may be homologous to human adrenarche.
Adrenal Glands↗
Pubertal endocrinology of the baboon: adrenarche.
The concentration of the adrenal steroids dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHA-S) was measured by radioimmunoassay in plasma of 134 baboons (Papio cynocephalus) from 0 to 17 yr of age. Plasma androstenedione (delta 4-A) was also measured in 289 baboons encompassing the same age range. The concentration of DHA was persistently high from birth to adulthood, exceeding 700 ng/dl at all ages. This differs markedly from the human pattern in which DHA concentrations fall below 50 ng/dl following regression of the fetal adrenal. Plasma DHA-S declined rapidly during the first 2 yr of life, causing a significant age-related decline in the ratio of DHA-S:DHA, a pattern not seen in man. Plasma delta 4-A declined during the first 3 yr, but remained greater than 100 ng/dl. delta 4-A then rose sharply at age 4, the time of gonadal maturation in the baboon. Thus, the baboon differs from man primarily in the persistent elevation of plasma DHA and delta 4-A prior to puberty. It remains to be determined whether this difference reflects fundamentally different mechanisms regulating adrenal androgen secretion or merely the closer temporal juxtaposition of fetal adrenal regression and adrenarche due to the more rapid sexual maturation of the baboon.
Aging↗
The developmental changes in plasma adrenal androgens during infancy and adrenarche are associated with changing activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase.
The plasma concentrations of dehydroepiandrosterone, androstenedione, and dehydroepiandrosterone sulfate decrease during the first year of life, remain low during childhood, and then increase during adrenarche. To determine whether alterations in adrenal enzyme activity might explain the changing secretory pattern of the adrenal androgens, we measured human adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase, 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase activities. 12 adrenals from individuals aged 3 mo to 60 yr were studied. The patients were divided into three groups based upon the age of the patient when the adrenal glands were obtained: group 1, infants aged 3--8 mo (n = 3); group 2, preadrenarchal or early adrenarchal children aged 2--9 yr (n = 4); and group 3, adults aged 20--60 yr (n = 5). The mean activity of the 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase fell by 50% and that of 3 beta-hydroxysteroid dehydrogenase-isomerase activity rose 80% from group 1 to 2. A fourfold increase in 17,20-desmolase (P less than 0.002) and 17-hydroxylase (P less than 0.001) activity and a doubling in 21-hydroxylase activity (P less than 0.005) occurred between groups 2 and 3. We conclude that the decline in plasma adrenal androgens after birth appears to be associated with a rise in 3 beta-hydroxysteroid dehydrogenase-isomerase and a fall in 17,20-desmolase and 17-hydroxylase activity. The subsequent increase in plasma adrenal androgen concentration during adrenarche is coincident with a rise in 17,20-desmolase and 17-hydroxylase activity.
3-Hydroxysteroid Dehydrogenases↗
Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats.
2-Hydroxyestrone (2-OHE1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE1 displaces saturably bound [3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17 beta-estradiol (E2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE1 to be apparent at doses roughly 20-50 times the minimum effective dose of E2. Instead, at doses of 2-OHE1 1000 times an effective dose of E2, no uterotropic effect was observed. When 2-OHE1 was injected together with E2 at dose ratios of 500:1, there was no antagonism of the effect of E2. To examine this discrepancy, the plasma MCRs (MCRpS) of E2 and 2-OHE1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE1 and E2 during control and infusion periods were measured by RIAs. The MCRp of 2-OHE1 averaged 50,000 ml/h, more than 100 times that of E2 (approximately 400 ml/h). The extraordinarily high MCRp of 2-OHE1 may explain the failure to observe any biological effects of this catechol estrogen, even at high doses. This rapid metabolism, presumably occurring in the blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.
Animals↗
A seminiferous tubular factor is not obligatory for regulation of plasma follicle-stimulating hormone in the rat.
Plasma testosterone, FSH, and LH levels were measured by RIA in sham-castrate control rats and in castrate male rats with testosterone-containing Silastic capsule implants to evaluate the relative contribution of testosterone and inhibin in maintaining normal FSH secretion in vivo. Silastic capsules maintaining normal testosterone levels maintained normal levels of both FSH and LH over the 5-day course of these studies. The data suggest that testosterone or its metabolites can account for at least 78%, and possibly all, of the FSH-suppressing activity of the testis. The data do not support an obligatory role for other testicular factors, such as inhibin, in the regulation of plasma FSH when normal testosterone levels are maintained.
Animals↗
Therapeutic use of pituitary desensitization with a long-acting lhrh agonist: a potential new treatment for idiopathic precocious puberty.
A two year girl with idiopathic true precocious puberty was treated with a long-acting LHRH agonist, D-Trp6-Pro9-NEt-LHRH (LHRHa). Prior to therapy, the patient demonstrated pulsatile gonadotropin secretion during both night and day, a pubertal response to exogenous LHRH, and an elevated plasma estradiol level. After eight weeks of therapy (4 microgram/kg daily), a mean gonadotropin levels fell to the prepubertal range, there was no evidence of pulsatile discharge of gonadotropins nor any response to exogenous LHRH, and plasma estradiol levels became undetectable. No adverse drug reactions were encountered and all effects of therapy were reversed following cessation of treatment for two months. LHRH analogs may offer a new approach to the therapy of idiopathic precocious puberty and merit further study.
Child, Preschool↗