Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hirsutism in adolescent girls commonly starts as an esthetic problem in young women and is later complicated by the development of infertility and polycystic ovary syndrome, which are frequent consequences of prolonged hyperandrogenism. To ascertain whether particular prepubertal clinical manifestations may predict the development of adolescent hirsutism, we followed 70 girls with precocious pubarche (PP) with or without prepubertal hypertrichosis (PH) until 3 years (mean age 14.8 +/- 0.9 years) after menarche. Similar follow-up was carried out in six girls with PP secondary to 21 hydroxylase deficiency (NC-CAH), treated with hydrocortisone. In addition, a retrospective study on the incidence of precocious pubarche was performed in 139 hirsute teenagers (mean age 17 +/- 1.8 years). Testosterone, androstenedione, dehydroepiandrosterone sulphate, 17 alpha-hydroxyprogesterone (basal and after ACTH), luteinizing hormone and follicle-stimulating hormone were evaluated by radioimmunoassay or immunoradio metric assay in the early follicular phase, in cycling subjects. Pelvic ultrasonography was also performed. In the 139 hirsute teenagers, 29 had a history of PP (21% vs. 0.6% in the general Italian population). Of these 139 patients, NC-CAH was diagnosed in 8 (6%), 5 of whom (63%) had PP. Of the 70 girls with PP, hirsutism was present in 44 (63%). PH was present in 37 of 44 patients (84%) with hirsutism, but only in 9 of 26 (35%) without hirsutism. Our results showed that 1) PP represents a risk factor for the development of postpubertal hirsutism; 2) the association with PH seems to increase the risk probability; and 3) patients with hirsutism due to NC-CAH have a higher incidence of PP compared with other hirsute patients, but glucocorticoid treatment in such patients prevents the development of hirsutism. Whether early treatment in the other PP patients may prevent the development of hirsutism remains to be established.
Steroids
PMID:Hyperandrogenism in the adolescent female. 961 92

The possibility that non-ACTH proopiomelanocortin-derived fragments may stimulate aldosterone production has previously been studied using nonhuman cells with inconsistent results. We have examined the response of aldosterone to beta-endorphin (beta-End) and joining peptide (JP) and compared these with the response to ACTH using eight cell suspensions prepared from human adrenal glands. ACTH, 10(-6), 10(-8), and 10(-10) M, consistently stimulated aldosterone accumulation above that occurring in unstimulated cells (150 +/- 83, 120 +/- 62, and 77 +/- 32 fmol/10(4) cells above basal, respectively; mean +/- SE; p < 0.05). beta-End significantly stimulated aldosterone production at 10(-6) and 10(-8) M (114 +/- 84 and 50 +/- 24 fmol/10(4) cells above basal; p < 0.05); 10(-10) M beta-End did not provide significant stimulation. Furthermore, JP stimulated aldosterone biosynthesis (41 +/- 16 fmol/10(4) cells above basal; p < 0.05), only at the highest concentration used, 10(-6) M. The addition of 10(-8) M ACTH plus 10(-6) and 10(-10) M beta-End to human adrenal cells yielded values significantly greater than those achieved with either agent alone (267 +/- 152 and 183 +/- 89 fmol/10(4) cells above basal; p < 0.05). These data indicate for the first time that beta-End and JP have the capacity to stimulate aldosterone production in human adrenal cells in vitro. The physiological and potential clinical significance of these observations has yet to be elucidated.
Steroids 1998 Sep
PMID:Non-ACTH POMC fragments stimulate aldosterone production by human adrenal cells in vitro. 972 92

This study presents the reactions of adrenocorticosteroids (cortisol and aldosterone) and sex steroids [testosterone, androstenedione, and dehydroepiandrosterone and its sulfate (DHAS)] 1) to a dexamethasone (Dex) treatment, which is expected to lower steroid levels via the ACTH blockade, and 2) to an exercise bout at maximal O(2) consumption, which is expected to increase steroid production via ACTH stimulation. Consistent with the decrease in ACTH, all steroids except testosterone reacted negatively to Dex, independently of the dose (0.5 and 1.5 mg administered twice daily for 4.5 days). After exercise, plasma ACTH rose to 600% of basal value, resulting in a significant increase in aldosterone and adrenal androgens, but cortisol and DHAS were unaffected. This apparently surprising result can be explained by differences in peripheral metabolism: a theoretical calculation predicted that after 15 min the increase in hormone concentration may only reach 12% for cortisol and 2% for DHAS. For cortisol and adrenal androgens, assays were carried out using plasma and saliva. The consistent results obtained from the two matrices allow us to consider salivary assays as a useful tool for steroid abuse detection.
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PMID:Dexamethasone in resting and exercising men. II. Effects on adrenocortical hormones. 1040 73

In very premature infants of less than 30 weeks gestational age there is no correlation between the severity of illness and plasma cortisol concentrations. Low plasma cortisol levels were measured during critical illness with severe arterial hypotension requiring catecholamine treatment in the first two weeks of life. Thus, a relative adrenal insufficiency is suspected. The pituitary responds to CRH and the adrenal cortex to ACTH. But it is still questionable, wether the response is sufficient. Preterm infants with an impaired adrenal function in the first weeks of life seem to be at a higher risk for developing bronchopulmonary dysplasia. Steroids are effective in the treatment of arterial hypotension and bronchopulmonary dysplasia. Because of the broad spectrum of severe and long-term adverse effects, the treatment with glucocorticoids is recommended only after carefully balancing its benefits and risks.
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PMID:[Adrenal function in very preterm infants in the early postnatal period]. 1171 6

The efficacy of ACTH, particularly in high doses, for rapid and complete elimination of infantile spasms (IS) has been demonstrated in prospective controlled studies. However, the mechanisms for this efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system have been attributed to activation of glucocorticoid receptors. The manner in which activation of these receptors improves IS and the basis for the enhanced therapeutic effects of ACTH--compared with steroids--for this disorder are the focus of this chapter. First, a possible "common excitatory pathway," which is consistent with the many etiologies of IS and explains the confinement of this disorder to infancy, is proposed. This notion is based on the fact that all of the entities provoking IS activate the native "stress system" of the brain. This involves increased synthesis and release of the stress-activated neuropeptide, corticotropin-releasing hormone (CRH), in limbic, seizure-prone brain regions. CRH causes severe seizures in developing experimental animals, as well as limbic neuronal injury. Steroids, given as therapy or secreted from the adrenal gland upon treatment with ACTH, decrease the production and release of CRH in certain brain regions. Second, the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors is considered, focusing on the effects of ACTH on the expression of CRH. Experimental data showing that ACTH potently reduces CRH expression in amygdala neurons is presented. This downregulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced downregulation of CRH expression, providing direct evidence for the involvement of these receptors in the mechanisms by which ACTH exerts this effect. Thus, ACTH may reduce neuronal excitability in IS by two mechanisms of action: (1) by inducing steroid release and (2) by a direct, steroid-independent action on melanocortin receptors. These combined effects may explain the robust established clinical effects of ACTH in the therapy of IS.
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PMID:ACTH treatment of infantile spasms: mechanisms of its effects in modulation of neuronal excitability. 1204 Aug 92

To evaluate the effect of a progestinic-estrogenic combination on human adrenal function 2 different ratios were given, 1 pill a day for 20 consecutive days from Day 5 to Day 24 of the ovarian cycle. Medroxyprogesterone acetate, 5 mg, with ethinyl estradiol, 50 mcg, (MAP-5-EE-50) and medroxyprogesterone acetate, 2 mg, with ethinylestradiol, 75 mcg (MAP-2-EE-75) were given to 8 women. Adrenal function was determined before, during, and after therapy and urinary 17-ketosteroids (17-KA), 17-hydroxycorticosteroids (17-OHCS), pregnanediol and pregnanetriol were measured. To stimulate the adrenals iv infusion of .25 mg synthetic ACTH was administered over a period of 6 hours. Stimulation of the pituitary-adrenal axis was done by giving 4.5 gm metopirone in 6 doses in 1 day. In all subjects a definite increase of plasma corticoids was found after 20 days of therapy. In 6 of the 8 cases a definite decrease of urinary 17-OHCS was observed. Pregnanetriol excretion decreased in all cases. Pregnanediol excretion, as determined in the urine throughout the luteal phase of the ovarian cycle, was decreased by both dosages, indicating a blockage of ovulation. Urinary excretion of tetrahydrocortisol and tetrahydrocortisone was decreased in all 5 cases studied. To investigate possible change in cortisol metabolism the percentage of free and conjugated 17-OHCS was determined in 4 cases. Values were unchanged. Half-life of injected cortisol was increased and secretion rate of endogenous cortisol reduced. Added tritiated cortisol in vitro has shown a higher cortisol binding capacity of human plasma after progestinic-estrogenic therapy. Administration of ACTH in 3 cases showed an adrenal response equal to that obtained before treatment, indicating adrenal reserve had been maintained. Hypothalamic-pituitary-adrenal function, as determined with metropione, showed a decrease of urinary adrenal metabolites in all cases. Results show that the 2 doses given block ovulation and that progesterone is not produced by a corpus luteum. The progestinic-estrogenic therapy, in both doses, modified the metabolism of cortisol in the same way as estrogens alone do.
Res Steroids (Amst) 1966
PMID:Effect of a progestinic-estrogenic combination on human adrenal function. 1230 25

The main groups of drugs that affect male libido, potency, sperm production, structure and function are summarized and their mechanisms described when known. About 15% of the 200 most commonly prescribed drugs can have adverse effects on male reproduction. Sedatives, tranquilizers, hypnotics, antiandrogens and the common antihypertensive methyldopa can depress libido. Spironoacetone has been reported to impair libido, potency, sperm count and motility, although reversibly. The phenothiazines and tricyclic antidepressants may induce prolactin secretion and consequent gynecomastia. Narcotics and hallucinogens influence male sexual performance. Morphine and methadone decrease LH and testosterone, and increase prolactin. Cannabis, hashish and marijuana initially increase libido and potency, but chronic use causes sexual inversion. Chronic alcoholism also may upset testosterone metabolism, causing testicular atrophy. Cyclophosphamide, used for nephrotic syndrome, and nitrofurans, used as food preservatives, cause direct damage to seminiferous tubules. Synthetic oganochlorine pesticides, especially DDT, have also been reported to damage spermatogenic cells directly, when injected in mice. Steroids such as ACTH, hydrocortisone and dexamethasone may inhibit steroidogenesis in animals.
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PMID:Effect of pharmacological agents on male reproduction. 1234 6

We examined fetal sheep adrenal glands from 99 to 130 days of gestational age (dGA) to see how connexin 43 (Cx43), the major if not the only adult adrenal gap junction protein, changes expression as the adrenal cortex emerges from the well-documented refractory period to participate in labor and delivery. Immunocytochemical technique and Western blot were used to examine changes in the quantity and quality of Cx43. In addition, adrenal glands of ACTH infused fetuses or of fetuses from dexamethasone injected ewes underwent image analysis quantification after Cx43 immunostaining. Finally, fetal adrenal glands, from fetuses splanchnic nerve sectioned (SPLX) at 125 dGA, were examined for the pattern of Cx43 immunostaining at 131 days of gestation. From 100 to 130 dGA, the amount of Cx43 in cells of the adrenal cortex increased steadily while the pattern of immunoreactivity changed from predominantly cytoplasmic to membrane bound. At 100-103 dGA, ACTH infusion increased the size of the cortex, but decreased the expression of Cx43 per unit area while dexamethasone had no effect on either parameter. Lastly, the expression of Cx43 as a membrane bound protein was not delayed or reversed by SPLX. We conclude that the described changes in Cx43 are most intriguing given their temporal relationship to the described preparturient increases in ACTH and cortisol in peripheral fetal plasma as term approaches and deserve further investigation.
Steroids 2003 Sep
PMID:Connexin 43 ontogeny in fetal sheep adrenal glands. 1295 66

This paper collates and reviews a number of clinical cases published over the last 20 years that we believe describe a novel steroid disorder associated with genital ambiguity. The authors of the original papers were unable to diagnose their patients conclusively. Females with the disorder are frequently masculinized and males feminized. The central feature of steroid biosynthesis is overproduction of pregnenolone and progesterone, which results in elevated concentrations of these steroids in plasma and exaggerated response to ACTH. Equivalent urinary data show elevated excretion of 5-pregnene-3beta,20alpha-diol (the major pregnenolone metabolite) and pregnanediol. Another notable feature of the metabolome is the relatively high plasma concentrations of the analytes for 21-hydroxylase deficiency (17-hydroxyprogesterone) and 17-hydroxylase deficiency (corticosterone). Correspondingly, metabolites of these steroids are prominent in urine. Circulating cortisol was generally normal but had blunted response to ACTH. Taken together these features pointed to an apparent relative deficiency of 21- and 17-hydroxylation, but no mutations have been found in the enzymes responsible for these transformations in cases where it has been investigated. The simultaneous presence of mutated genes on two chromosomes is also extremely unlikely. Until more is known of this interesting condition, and the genetic cause (presumed) is known, we propose naming it apparent pregnene hydroxylation deficiency (APHD). The metabolome is similar to that of isolated 17,20-lyase deficiency with which it has been confused. In fact, diminished (but not isolated) lyase activity is probably a significant factor in some patients. We believe that the attenuated steroid hydroxylation could be associated with deficiency of the required co-factors and modulators of hydroxylation such as P450 reductase and cytochrome b5. Post-translational modifications of the hydroxylases such as phosphorylation/dephosphorylation have also been suggested as influential in directionally regulating steroid synthesis. Some patients with the disorder have no dysmorphology apart from genital malformations while others have skeletal abnormalities attributed to Antley-Bixler syndrome. Whether we are looking at different conditions, or a severity continuum is not known. It is possible that the presence of this metabolome may become a required feature for diagnosis of Antley-Bixler syndrome. A combination of intersex phenotype and dysmorphology suggests that an error in a transcription factor may be an alternative to hydroxylation redox partner deficit as causative of the condition.The virilization of female patients with APHD probably results from a transient hyperandrogenism prior to birth.
Steroids 2003 Oct
PMID:Apparent pregnene hydroxylation deficiency (APHD): seeking the parentage of an orphan metabolome. 1462 2

Since the original description of the structure of the antiprogestin, mifepristone, was published, numerous related compounds have been synthesized which may function as progesterone antagonists (PAs) or progesterone receptor modulators (PRMs). The latter are mixed agonists-antagonists. Both PAs and PRMs have therapeutic applications in female health care. Mifepristone is predominantly a PA and displays only minimum agonist activity in certain systems. Together with a prostaglandin, mifepristone can terminate pregnancies of less than 9 weeks duration, and it may also be used at later gestational ages. Mifepristone causes expulsion of the uterine contents following intrauterine fetal death. A mifepristone-prostaglandin combination has been shown to be very effective treatment in women with menses delay of 11 days or less. Many PAs and PRMs display antiproliferative effects in the endometrium. Serum estradiol levels however remain in the early to mid-follicular phase range. For this reason, they have application in the treatment of endometriosis and myoma without being associated with bone loss and hypoestrogenism. PRMs may also find application in the treatment of dysfunctional bleeding as well as an adjunct to estrogens in hormone replacement therapy in postmenopausal women. Many PAs have contraceptive potential by suppressing follicular development and blocking the LH surge. Low doses may also be potential contraceptives by retarding endometrial maturation without affecting ovulation or inducing bleeding. Mifepristone is an excellent agent for use as an emergency "postcoital" contraceptive. PAs may also be useful in IVF programs to prevent a premature LH surge and to delay the emergence of the implantation window. In addition to their use in women's health care, mifepristone and several other PAs are potent antiglucocorticoid agents and may be used to treat ACTH-independent Cushing's syndrome. They may also be used in the treatment of tumors containing steroid receptors and in other situations which require suppression of the ACTH-cortisol axis.
Steroids 2003 Nov
PMID:Progesterone antagonists and progesterone receptor modulators: an overview. 1466 91


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