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Biomedical subjects

M G Forest

Publications and source records attributed to M G Forest.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effects of drug administration on gonadotropins, sex steroid hormones and binding proteins in humans.

The possible mechanisms by which the administration of drugs may alter the gonadal function in humans are considered in this review. Based on personal data, and on data published in the literature, the following events may occur: (1) blockade of gonadal steroidogenesis; (2) interaction of drug(s) with the steroid-binding protein system in plasma, and (3) interference of drug(s) at the level of the feedback control of gonadotropin secretion. Representative examples of the above mechanisms are as following: (1) Ketoconazole possesses inhibitory effects in vitro on cytochrome P-450. When given in adult males, it decreased the plasma concentrations of testosterone (T) and androstenedione and increased 17 alpha-hydroxyprogesterone levels, suggesting that this drug acts in vivo on gonadal steroidogenesis by blocking the 17,20-lyase. (2) Danazol is a progestagen with high affinity for sex steroid-binding protein (SBP); when given in high dosages in normal males, it increased rapidly the dialyzable fraction (percent protein unbound or free fraction) of T. This suggests that by interacting with the binding sites of SBP, danazol and/or its metabolites displace the fraction of T bound to SBP. However, in males as well as in females, the long-term administration of danazol decreased also the binding capacity of SBP, and consequently increased the free fraction of sex steroid hormones. (3) Dihydrotestosterone (DHT), the most active androgen in many target cells, given at therapeutic dosages to adult males, resulted in a decrease in plasma concentrations of luteinizing hormone (LH) and T, without any significant change in the percent of free T, even though the affinity of DHT for SBP is higher than that of T. This suggests that the main effect of DHT is to inhibit gonadotropin secretion at the central level. (4) Flutamide, a nonsteroidal antiandrogen, increased both LH and T levels, demonstrating its pure antiandrogenic activity on gonadotropin secretion. The consequence(s) of the effects of such drugs on the production, the metabolic clearance rate and the bioavailability of sex steroid hormones are discussed.

Androgens↗
PubMed1987

[Second prenatal diagnosis in a familial form of male pseudohermaphroditism caused by 17 keto-reductase deficiency: prediction confirmed by a normal third male infant].

In the first child of this family, the diagnosis of male pseudo-hermaphroditism due to 17 keto-reductase deficiency was established at two months of age after HCG test. During the second pregnancy, amniocentesis was performed for fetal karyotype and steroid determination in the amniotic fluid: an affected male fetus was suspected and this prediction was confirmed at birth. For the third pregnancy, a prenatal diagnosis was requested again and made, according to the same procedure: a normal male fetus was predicted and this diagnosis was confirmed at birth; this study demonstrates the feasibility and reliability of a prenatal diagnosis for 17 keto-reductase deficiency.

17-Hydroxysteroid Dehydrogenases↗
PubMed1987

[An XX male newborn infant. A genetic and endocrinologic study].

The second child of a non consanguineous couple had a male phenotype with two intrascrotal testes of normal size however a scrotum bifidum was noted. The karyotype of the child was 46 XX and the parents one's was normal. No Y specific sequence was detected by using four Y specific probes (47 B, 12 F3, 52 D and 118). During the first semester of life, hormonal investigations showed a normal testicular function.

Androgens↗
PubMed1986

Usefulness of plasma pregnenolone sulfate in testing pituitary-adrenal function in children.

In normal subjects, plasma pregnenolone sulfate (PS) levels high at birth, decreased during the first year of life in relation to the pattern of involution of the fetal adrenal zone. Thereafter, PS levels, in contrast with those of DHAS, did not show the abrupt rise characteristic of the adrenarche, but increased very progressively till adulthood. The response of PS to various provocative tests of adrenal and pituitary function (ACTH and Metyrapone stimulation, dexamethasone suppression), has been established in normal subjects. The measurement of plasma PS levels in basal conditions as well as in response to dynamic tests was very useful in the diagnosis of various adrenal and pituitary diseases in children.

Adolescent↗
PubMed1985

Althesin interaction with human plasma steroid binding globulins.

The binding affinities of two steroid anaesthetics, alphaxalone (Alfx) and alphadolone acetate (Alfd), for testosterone-oestradiol-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were measured in human serum. In 8 male patients, the effect of i.v. administration of Althesin (a mixture of Alfx and Alfd) on the transport of testosterone (T) and cortisol (F) was studied. Both Alfx and Alfd bind to TeBG and CBG with a relatively high affinity (10(6)M-1). A significant change in the percentage of unbound T was observed during Althesin infusion, with no change in total T concentration or in the TeBG binding parameters. The results suggest that by interaction with TeBG binding sites Alfx and/or Alfd displaced T bound to TeBG, and transiently increased the percentage of unbound T. A significant increase in the concentration of F was observed during althesin infusion, while the percentage of unbound F and the CBG binding parameters were unchanged. The dose of Alfx and Alfd used was not sufficient to alter the transport of F during brief althesin anaesthesia in men.

Adolescent↗
PubMed1985

Sexual maturation of the hypothalamus: pathophysiological aspects and clinical implications.

Sexual maturation in humans begins early in fetal life and culminates in adulthood when the gonads have acquired a full capacity for reproduction. It is remarkable that during this long process, the pituitary gonadal function, hence its hypothalamic control presents an alternative of activation and inhibition periods, during which the interrelations of the 3 components of the hypothalamic-pituitary-gonadal axis change gradually and inversely. The ontogeny of the hypothalamic-pituitary system, the varying activity of the reproductive endocrine system throughout sexual maturation and the developmental changes in the interrelations of the hypothalamic-pituitary-gonadal axis are reviewed: the most striking feature of human sexual development is the long inhibition of hypothalamo-pituitary function during childhood. Much indirect evidence points to the determining role of the CNS in the maturation of hypothalamic function: the occurrence of rhythms of secretion, the amplitude of secretions and peripubertal specific sleep-related nycthemeral rhythm of secretion at the onset of puberty. Despite the reality of a negative feedback control, these changes do occur independently of gonadal secretions since they are observed (qualitatively if not strictly quantitatively) in agonadal children. It is likely that neurotransmitters (dopamine, serotonine) and opiates have an inhibitory effect on Gn-RH release. But we still don't know their evolution during sexual maturation. It does not appear that melatonine plays any determinant role in the onset of human puberty. The clinical implications of our present understanding of the physiological events occurring during sexual maturation are several. Considering the major problems related to abnormal sexual maturation we will discuss successively: (1) diagnosis of hypogonadotrophic hypogonadism in early infancy; (2) differential diagnosis between premature thelarche and true sexual precocity; (3) the usefulness of endocrine investigations in the evaluation of hypothalamic-pituitary function; and (4) the new developments in the treatment of precocious puberty, delayed puberty or hypogonadism.

Adolescent↗
PubMed1985

Secretion of anti-Müllerian hormone by immature bovine Sertoli cells in primary culture, studied by a competition-type radioimmunoassay: lack of modulation by either FSH or testosterone.

Secretion of anti-Müllerian hormone (AMH) by immature bovine Sertoli cells in primary culture was studied through a competition-type RIA employing a polyclonal antibody and 125I-labelled purified AMH. This RIA is approximately 10 times more sensitive than the solid-phase two-site monoclonal antibody-based RIA described previously. Biosynthesis and secretion of AMH by cultured Sertoli cells require approximately 48 h, are not influenced by FSH or testosterone and steadily decrease over a one-week period of culture. Cyclic AMP response to FSH stimulation is normal in cultured cells. Whether the factors responsible for the extinction of AMH production in vitro are in any way related to those operating during normal maturation, which lead to repression of AMH biosynthesis in adult Sertoli cells, is not known at the present time and deserves further study.

Age Factors↗
PubMed1985

[Prenatal diagnosis in a familial form of male pseudohermaphroditism due to 17-keto reductase deficiency].

In an infant considered at birth as a female but with easily palpable gonads in the labia major, the XY karyotype and the endocrine studies (determination of plasma levels of steroid hormones under basal conditions and during hCG stimulation) were consistent with the diagnosis of male pseudohermaphroditism due to 17-keto reductase deficiency. During the second pregnancy an amniocentesis revealed a 46 XY karyotype. Endocrine studies performed on the amniotic fluid at midgestation suggested that the fetus was affected by the same enzyme defect. After birth, the diagnosis was demonstrated with anatomical an endocrine studies.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

[Kinetics of the testicular steroidogenic response to stimulation by placental gonadotropin hormone. VI. Enzyme deficiencies of testicular biosynthesis].

The kinetics of the responses of plasma testosterone (T) its precursors and estrogens to a single injection of human chorionic gonadotropin (hCG) was studied in 9 46 XY subjects affected with one of 4 inborn errors of testicular biosynthesis. In the adults (n = 4), the kinetics and profile of the hormonal responses to hCG were qualitatively comparable to those previously described in normal adult men, and the profile of response characteristic of the hCG-induced steroidogenic desensitization was observed, suggesting that the 17,20 desmolase blockade induced by hCG is superimposed to the inborn enzymatic defect. In the prepubertal patients (n = 5), testicular desensitization was not observed, as in prepubertal controls. However, T precursors, each marker of a given enzymatic blockade, significantly rose several fold 2-5 days after the hCG injection, while they do not in normal children. The results also show that an hCG test is necessary for a clear-cut diagnosis of a given enzymatic block in children, but is not in adults. The single hCG injection protocol used in this study offers a sophisticated way of a qualitative analysis of the testicular secretory products, but is not a must.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Ultrastructural evidence for endogenous testosterone immunoreactivity in the pituitary gland of the rat.

Several attempts have been made to localize steroids by means of immunocytological techniques. However, these methods were found inadequate for detecting steroids bound to their receptors. To localize endogenous testosterone (T) in its target cells at the ultrastructural level, an immunocytological technique was performed on ultrathin sections obtained by cryo-ultramicrotomy. T was detected in the pituitary glands obtained from intact male or female rats and castrated rats, but not in castrated + adrenalectomized rats. Animals were also injected either with testosterone, with other steroids (estradiol, progesterone, corticosterone) or with an androgen antagonist (cyproterone acetate). In addition, some ultrathin sections were preincubated either with phosphate buffers of various pH, corticosterone, cyproterone acetate solution, or with T solution. The content of T in the pituitary before and after fixation was measured by radioimmunoassay; it decreased after fixation. T immunoreactivity was localized in the gonadotropic cells only, both in the male and female rats. At the subcellular level, the immunoreactivity was detected in the cytoplasmic matrix and in the nucleus. Immunoreactive T disappeared 1) in rats after castration + adrenalectomy; by means of radioimmunoassay no T was measured in these pituitary glands; 2) in rats injected with 25 micrograms/rat of cyproterone acetate; 3) after preincubation of pituitary sections on a drop of cyproterone acetate (1 X 10(-6) M). The immunocytological reaction was not modified when the rats were injected with estradiol, progesterone or corticosterone (1 mg/rat), or after preincubation of the sections with corticosterone (1 X 10(-3 M), or a buffer solution at pH 7.6. Lower or higher pH values led to a strong decrease in the immunoreactivity. After injection of T (15 micrograms/rat) the immunocytological reaction was more abundant in the nucleus and less in the cytoplasm. The immunoreactivity was again observed when the sections were preincubated with cyproterone acetate solution and then with T solution. These data suggest that T can be detected by means of immunocytochemistry. It is probably bound to a specific binding site.

Adrenal Glands↗
PubMed1984

17,20-desmolase deficiency in a female newborn, paradoxically virilized in utero.

The patient was born with ambiguous genitalia (stade III of Prader). The karyotype revealed a normal female genotype. A defect in 21-hydroxylase, at first suspected, was denied by the hormonal studies. Indeed, extremely high levels of pregnenolone, pregnenolone sulfate, progesterone were found in association with low plasma levels of delta 4-androstenedione, testosterone, dehydroepiandrosterone and its sulfate, while cortisol 17OH-progesterone and ACTH levels and plasma renin activity were normal. The hormonal pattern was thus consistent with 17,20-desmolase deficiency. The dynamic studies further supported this contention: all the progestagens rose further after ACTH stimulation and were suppressed by dexamethasone. Meanwhile, all androgens failed to rise after ACTH: the responses of cortisol were normal. The in utero virilization of the female fetus was not understood until an history of virilization was allegedly found in the mother (luteoma of pregnancy). This is the first case of 17-20 desmolase defect recognized in a female newborn. This child, born with ambiguous genitalia had presented the concurrence of two very rare conditions. The in utero virilization of maternal origin enabled us to make the diagnosis of the 17-20 desmolase defect, which otherwise would have been ignored in a XX subject in the neonatal period because it would obviously be unsymptomatic at this age.

Adrenocorticotropic Hormone↗
PubMed1984

Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency.

In an attempt to prevent in utero virilization of female fetuses with 21-hydroxylase deficiency, six mothers at risk were treated with either hydrocortisone (n = 1) or dexamethasone (n = 5) in early pregnancy. Treatment was continued to term in the two pregnancies in which the diagnosis of an affected female fetus was confirmed. In patient 1 (hydrocortisone treatment) fetal adrenal suppression was only partial but the external genitalia were only slightly abnormal. In patient 2 (dexamethasone treatment) fetal adrenal suppression was achieved and the external genitalia were normal at birth. These encouraging results open a new prospect for treating congenital adrenal hyperplasia in utero.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men.

Dihydrotestosterone (DHT) was administered percutaneously in a dose of 125 mg twice daily for 10 days to 12 normal men. Basal plasma levels of testosterone (T), 17 beta-estradiol (E2), and LH were measured every 2 days in these men and every 5 days in subjects from a control group receiving placebo. The daytime course of plasma hormone levels between two DHT applications was studied in six men. LRH tests were performed in nine men before and on day 10 of DHT administration. Plasma levels of free T and free E2, and T - E-binding globulin capacity and affinity were measured in six men before and on days 5 and 10 of DHT administration. Before DHT administration, there was no difference in basal plasma levels of T, DHT, E2, and LH between the control and the DHT-treated group. In the latter group, plasma DHT levels increased sharply from 0.52 +/- (+/- SE) to 3.70 +/- 0.92 ng/ml on day 2 (P less than 0.001) during DHT treatment. Plasma T, E2, and LH levels decreased significantly from 7.33 +/- 0.74 to 1.33 +/- 0.54 ng/ml (P less than 0.001), from 46 +/- 5 to 20 +/- 3 pg/ml (P less than 0.01), and from 7.8 +/- 1 to 4.2 mIU/ml (P less than 0.05), respectively. Except for a small decrease in plasma DHT (P less than 0.05) 12 h after the previous DHT application, hormone levels were stable during the time between the two DHT treatments. The responses of LH and FSH to LRH were not different before and on day 10 of DHT administration. Plasma levels of free T and free E2 as well as those of total T and E2 decreased; however, the percentages of unbound T and E2 were not different before and during DHT administration. T - E-binding globulin capacity and affinity were not modified by DHT administration. Changes in plasma DHT levels were negatively correlated with those in The results of this study demonstrate that 10-days DHT administration has an inhibitory effect on the hypothalamo-pituitary-testicular axis in normal men.

Adult↗
PubMed1984

[Kinetics of the steroidogenic response of the testis to stimulation by hCG. V. Blockade of 17-20 lyase induced by hCG is an age-dependent phenomenon inducible by pre-treatment with hCG].

The series of events, evidenced in animals after a single injection of human chorionic gonadotrophin (hCG): down-regulation of LH/hCG membrane receptors, uncoupling between receptors and the adenylate cyclase, also includes a blockade of testicular steroidogenesis beyond cyclic-AMP formation, including an inhibition of the 17 alpha-hydroxylase-17, 20-desmolase enzymatic complex. This complex phenomenon, named hCG-induced testicular desensitization also occurs in adult men. Since it is not known if and when these effects are initiated during sexual maturation, we have investigated the kinetics of responses of plasma testosterone (T), its two immediate precursors, delta 4-androstenedione (delta 4) and 17 alpha-hydroxprogesterone (OHP), and 17 beta-estradiol (E2) for a week after a single injection of hCG given at the same dosage (100 IU/kg body weight) in subjects not yet exposed to adult levels of endogenous LH, ie prepubertal boys and untreated hypogonadotrophic hypogonadic (HH) adult men. The HH subjects have been restudied after 3 months of a weekly injection of the hCG at the same dosage. In immature individuals, the effect of hCG on testicular steroidogenisis was strikingly different from that observed previously in adults: in the former, whether prepubertal boys or untreated HH adults, a single hCG injection induced a progressive and substantial rise in plasma T, maximal at 96-120 h, a modest and late rise in E2, but no significant change in delta 4 or OHP. In contrast, in adult men there is a dissociation between the responses of plasma T and delta 4 (maximal at about 72 h) to hCG and those of OHP and E2 which peak at about 24 h. After 3 months of hCG-treatment the adult pattern was induced in HH patients: early and significant rise in OHP and E2. This suggests that a pre-exposure to LH/hCG is necessary for hCG-induced testicular desensitization, at least for its enzymatic expression. A stimulatory effect of hCG on a testicular aromatase and an inhibitory effect on the 17, 20-desmolase are observed concomitantly in relation to age or to previous gonadotropin environment. It still remains uncertain to conclude that the former effect is directly responsible for the latter.

Adult↗