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Biomedical subjects

M G Forest

Publications and source records attributed to M G Forest.

At least 127 records · Page 7Linked to original sources
PubMed1978

Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production.

Plasma levels of dehydroepiandrosterone sulfate (DHAS) were measured in 513 normal full term newborns, infants, children, adolescents, and adults and the results were expressed in micrograms per dl. In infancy and childhood, DHAS levels were similar in both sexes. In 74 neonates, mixed cord blood mean values /+- SD were 134.6 +/- 64. During the first day of life, plasma DHAS levels were 140 +/- 125 in 33 neonates. During the first month of life, DHAS decreased drastically, then more progressively until the 6th month of life. Between 1-6 months of age, mean levels were 5.9 +/- 4.7 in 40 children. DHAS was very low between 1-6 yr of life (2.3 +/- 1.6) and rose abruptly at the 7th year of life. Thereafter, DHAS continued to increase correlatively with age and pubertal stages in both sexes, a further increase after age 16 or pubertal stage P5 was noted only in male subjects. In adults, DHAS was significantly higher in male (224 +/- 93) than in female (138.3 +/- 51) subjects. DHAS levels were compared to those of dehydroepiandrosterone; at two periods of life, early infancy and adulthood, their patterns differed. After long term hCG stimulation, DHAS increased significantly in 45 normal prepubertal boys and in 2 boys with adrenal insufficiency. These data would suggest a direct testicular production of DHAS.

Adolescent↗
PubMed1978

Age-related response of plasma testosterone, delta 4-androstenedione, and cortisol to adrenocorticotropin in infants, children, and adults.

The response of plasma testosterone (T), delta 4-androstenedione, and cortisol (F) to the administration of synthetic Zn beta 1-24 ACTH (0.5 mg/m2 im every 12 h for 3 days) was ascertained in 20 infants, 35 prepubertal children, 4 early pubertal boys, and 15 adults. At all ages and in both sexes, a significant rise in delta 4-androstenedione and F was observed (P less than 0.00001), whereas the response of T showed a sex difference: T levels increased in females (P less than 0.001) at all ages in response to ACTH, while they decreased (P less than 0.01) in males at periods of active testicular secretion (early infancy, puberty, and adulthood). In prepubertal boys, in the absence of significant Leydig cell activity, T levels increased after ACTH, as they did in girls. The post-ACTH values of T, expressed as percent-ages of the control levels, were significantly lower (P less than 0.01) in infants (3.17 +/- 16.7%) than in pubertal boys (59.5 +/- 14.6%) or adult men (57.9 +/- 7.7%). F levels were significantly higher after ACTH stimulation at 1-4 months of age (253 +/- 129 micrograms/dl) than at any later age studied (64 +/- 17 micrograms/dl). It would seem, therefore, that the suppressive effect of ACTh on testicular secretion might be glucocorticoid mediated and its magnitude might be related to circulating levels of F.

Adolescent↗
PubMed1977

[Comparison of plasma testosterone (T), androstenedione (A) and dhea variations after métopirone in 10 normal and 12 hirsute women (author's transl)].

Plasma testosterone; androstenedione and DHA were measured by radio-immunoassay before (J1) under (J2) and 24-hour after (J3) oral metyrapone (4,5 g) in 10 normal and 12 hirsute women. Although individual values were dispersed, hirsute women, as a group, had significantly higher values at each time for each steroid. Hirsute women with normal basal T had normal T and A values for J1, J2, J3; while these with elevated basal T had elevated T and A value for all samples. Plasma DHEA was elevated in the two groups, before, under and after métopirone.

Administration, Oral↗
PubMed1977

[Effects of clomiphene and estrogens on circulating gonadotropins, testosterone, androstenedione, in old menopausal women (author's transl)].

The threshold of sensitivity of the gonadostat has been tested in 20 old menopausal women by clomiphene (50 or 200 mg/day for 5 days) and/or low doses of ethinyl oestradiol (EE2) (10 or 20 microgram/day). Clomiphene did not increase nor decreased serum levels of LH-FSH and testosterone (T) but increased significantly androstenedione (A) levels. Even at the lower dosage used, EE2 decreased drastically the levels of LH but less completely that of FSH. Clomiphene breaks off partially the oestrogen's blockade on FSH but not on LH. No modification was observed for T and A even after 30 days of estrogen therapy. This data shows the peculiar sensitivity of the gonadostat in advanced menopaused women. It also suggests that the gonadostat exhibits a low threshold of sensitivity analogous to that observed in late prepubertal period. Moreover, the different behaviour of LH and FSH in response to the negative feedback of oestrogens supports that an ovarian factor, distinct from estrogens and missing during menopause plays a role in the regulation of FSH.

Clomiphene↗
PubMed1977

[Plasma androgens and maturation of the hypothalamo-pituitary-gonadal axis in infants and children (author's transl)].

The plasma androgens testosterone (T) and delta(4)-androstenedione (delta(4)) were measured by RIA in 245 children under 1 year of age, in 70 children of prepubertal age, and in 250 adolescents during puberty. The values presented in the tables, and their changing relation to each other, suggest, that 1. at birth T and delta(4) are of fetal origin demonstrating the important endocrine function of the fetal testis; 2. after 6 months of age there is no significant endocrine activity of the gonads any more; 3. the prepubertal activation of the adrenal androgens production (adrenarche) is similar in the 2 sexes but their chronology is different for each androgen: an increase is observed after age 8 for delta(4), after age 10 for T. 4. in puberty the increase of T- and delta(4)-values differs markedly according to the two sexes. So, while the gradual prepubertal maturation of androgen steroid production, passing the stage of "adrenal puberty", could be demonstrated convincingly, the role of the different androgens in the maturation of the "gonadostat" (hypothalamopituitary complex) still remains a matter of hypothesis.

Age Factors↗
PubMed1976

Leydig-cell agenesis: a cause of male pseudohermaphroditism.

We studied a 35-year-old patient with female external genitalia, primary amenorrhea and XY karytotype. Plasma testosterone was 10 ng per deciliter, which did not change after administration of human chorionic gonadotropin, increased to 22 ng per deciliter after ACTH, and decreased to 0.9 ng per deciliter after dexamethasone. Plasma delta 4-androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone were in the normal range. Plasma luteinizing hormone was high, but follicle-stimulating hormone normal (7.5 mlU per milliliter). There were two testes with epididymis and vas deferens, but no Mullerian structures. Microscopical examination showed hyalinization of tubules, which were lined by normal Sertoli cells and occasional immature germ cells. No Leydig cells were seen. After castration follicle-stimulating hormone increased to 43 mlU per milliliter. We conclude that this case of male pseudohermaphroditism was probably due to a Leydig-cell agenesis, that the epididymis and vas deferens can be developed in such a condition and the follicle-stimulating hormone secretion is regulated, at least in part, by a non-androgen substance secreted by Sertoli cells.

Adrenal Glands↗
PubMed1976

O-(Carboxymethyl)oxime steroidal haptens linked in the C3 position: study of the characteristics of antibodies against 17alpha-hydroxyprogesterone and testosterone and of their evolution with time.

The production of highly sensitive and specific antisera against 17alpha-hydroxyprogesterone (17 OHP) is reported. 17 OHP was rendered antigenic by covalent linkage to bovine serum albumin through position 3 of the steroid. An unambiguous method to prepare the mono-3-0-(carboxy-methyl) oxime derivative (CMO) of 17 OHP is described starting from 17 OHP-acetate. Antisera raised in rabbits were of high affinity for 17 OHP (Ka = 1 to 2 x 10(10) L/mole) and showed very little (less than 0.7%) or no cross reaction with a variety of steroids. Cross-reaction with 17alpha-hydroxy pregnenolone was however significant. When studied in relation to time, cross-reaction of the latter steroid decreased significantly (18 to 2%) while Ka remained at the same level. The same study of the evolution with time (up to 600 days) of the characteristics of antisera raised against the 3 CMO derivative of testosterone is also reported.

Animals↗
PubMed1976

Use of highly specific antibodies against 17alpha-OH-progesterone in a simplified nonchromatographic RIA and in the simultaneous determination of four sex hormones in human plasma.

A highly specific antiserum raised against the 3(O-carboxymethyl)oxime of 17alpha-hydroxyprogesterone (17-OHP) was produced in rabbit and used in the development of a specific radioimmunoassay (RIA) for 17-OHP which included a celite chromatography. Methods allowing the measurement of plasma 17-OHP levels either separately or in combination with that of several plasma androgens (testosterone, delta4-androstenedione and dehydroepiandrosterone) are described. Moreover, RIA meabsurement of plasma 17-OHP levels with or without chromatographic (celite column) purification gave comparable results (mean +/- SD) in 29 normal adult males (118 +/- 34 ng/100 ml) and 35 normal adult females (follicular phase: 46+/- 16 ng/100 ml); luteal phase: 241 +/- 71 ng/100 ml).

Adult↗
PubMed1976

Plasma adrenal and gonadal sex steroids in human pubertal development.

Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.

Adolescent↗
PubMed1976

Unconjugated dehydroepiandrosterone plasma levels in normal subjects from birth to adolescence in human: the use of a sensitive radioimmunoassay.

A specific and sensitive radioimmunoassay for measuring unconjugated plasma dehydroepiandrosterone (DHA) has been developed and the results expressed in ng/100 ml. Mean values +/-1 SD were in mixed cord blood 593.3 +/- 186.5 in 21 females and 712.7 +/- 190.9 in 18 males. During the first day of life the peripheral plasma concentration of DHA was 917.6 +/- 317.8 in 22 female and 922.65 +/- 290 in 17 male neonates. During the first month of age, DHA levels decreased significantly and then more progressively throughout the first year of life. Mean levels observed between the first and 6th month of life were 147.1 +/- 53.6 in 15 girls and 151.6 +/- 62.7 in 28 boys. Between 6 and 12 months of age mean DHA levels were 90.9 +/- 43.3 and 68.14 +/- 30.9 in 11 girls and 24 boys, respectively. In 250 normal children, plasma DHA levels were very low between 1 to 6 years of age, but rising progressively thereafter without any sex difference long before any clinical sign of puberty. A circadian rhythm parallel to that of cortisol was observed as early as 5 years of age. Acute and chronic stimulation of ACTH confirmed the adrenal origin of DHA, while the results of hCG stimulation test and fluoxymesterone suppression test assessed the testicular participation to the DHA production.

Adolescent↗
PubMed1976

Male pseudohermaphroditism with hypertension due to a 17alpha-hydroxylation deficiency.

A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17alpha-hydroxylase deficiency demonstrated by low cortisol (0-56 mg/24 h), high corticosterone (270 mg/24 h) and 11-deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol(1-8 ng/dl) were all low. Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure.

Acute Kidney Injury↗
PubMed1975

Differentiation and development of the male.

Male differentiation and development takes place against a tendency towards neutral or feminine differentiation. At each step of development male differentiation results from a suspension of a basic female development and the imposition of male features for which a normal functioning testis is necessary. Once the testis has differentiated early in gestation the establishment and maintenance of normal testicular function will condition male sexual differentiation and maturation. Nature likes to express herself in a rhythmic fashion (circhoral, ultradian, circadian, menstrual, long-term rhythms). To epitomise testicular function throughout development we would propose the term 'ontogenic rhythms' to describe the three periods of maximal testicular activity, fetal, neonatal and adult. This results in the differentiation which eventually determines adult sexual activity.

Androgens↗
PubMed1975

Time course of the effect of adrenalectomy on transcortin binding characteristics: appraisal of different methods of calculation.

The time course effect of adrenalectomy on the transcortin-corticosterone association constant (KT), its concentration of binding sites (ST) and the corresponding binding constant (SAKA) of albumin has been investigated by equilibrium dialysis at 37 C on plasma samples collected 0, 3, 6, 12, 24, 48, 96 and 144 h after adrenalectomy in male adult rats. The data have been analyzed by 3 different methods: a graphical Scatchard analysis using bound over unbound versus bound as representation axes and 2 least squares minimization methods in which axes were, respectively, bound over total versus mass of corticosterone added and total versus unbound. Confidence regions can be computed in the last two methods allowing the statistical comparison of the different dialysis experiments. Results obtained by the three methods are quite similar and led to the conclusions that following adrenalectomy KT was constant while ST varied. The observed pattern was a decrease until the first 24 h followed by a rise reaching almost twice the control value at 144 h. It would also appear that SAKA decreases slightly within 24 h following adrenalectomy.

Adrenalectomy↗
PubMed1975

Pattern of plasma testosterone and delta4-androstenedione in normal newborns: Evidence for testicular activity at birth.

Plasma testosterone (T) and delta4-androstenedione (delta) levels were measured by a sensitive and specific radioimmunoassay method in 157 blood specimens from normal neonates. In both sexes at birth plasma T and delta were significantly higher in peripheral than in cord blood and drop within the first week of life. In males a secondary increase in both T and delta had occurred by the 2nd week of life while values continue to decrease in females. The present data demonstrate that testicular activity is still present at birth and suggest that the transient fall in T levels likely due to the removal of chorionic gonadotropin (hCG) secretion is responsible for the secondary activation of the hypothalamic pituitary axis by a negative feed-back mechanism.

Androstenedione↗
PubMed1975

[Effect of the conditions of coupling in testosterone-albumine conjugates on the quality of the antibodies produced in the rabbit].

In order to produce antibodies against small molecules as steroid hormones a necessary step in the preparation of the antigen includes a covalent linkage of the hapten to a "carrier" protein. Two coupling procedures (mixed anhydrid method and carbodiimide method) have been utilized in the preparation of testosterone conjugate linked in the C3 position. The same batches of testosterone (o-carboxy methyl) oxime and crystallized bovine serum albumine have been used. In the 2 different antigens the steroid/BSA molar ratio was identical (30). Antibodies have been raised in female New-Zealand rabbits. It is concluded that experimental conditions of covalent linkage influenced the antigenic potency of the conjugate used. Antibodies of considerably higher titer, capacity and affinity were obtained when the mixed anhydrid method was used. However the specificity of these antibodies did not appear to be influenced by the type of antigen used.

Anhydrides↗