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Biomedical subjects

D Apter

Publications and source records attributed to D Apter.

At least 55 records · Page 3Linked to original sources

Serum sex hormone-binding globulin during puberty in girls and in different types of adolescent menstrual cycles.

Serum sex hormone binding globulin (SHBG) concentrations were measured by an immunoradiometric assay, as part of a longitudinal study of puberty in girls, and were related to age, pubertal stage, age at menarche, weight, nature of the menstrual cycle and serum concentrations of sex steroids. A slow but very significant decrease was seen in SHBG from 77 nmol/l at 8-10 years of age to about 50 nmol/l after 15 years of age. Serum SHBG concentrations showed weak negative correlations with those of androstenedione and testosterone during puberty. The closest associations found between SHBG and the parameters measured were negative correlations with weight and body fat percentage in both pre-menarcheal and post-menarcheal girls, even after the effect of age was accounted for by calculating partial correlation coefficients. Girls who experienced early menarche (before 13.0 years) had lower SHBG but higher oestradiol serum concentrations at 10.0-15.9 years of age compared to girls with later menarche. In ovulatory menstrual cycles, a significant increase in SHBG was found from the early to the late part of the cycle, whereas no changes took place in anovulatory cycles. Serum concentrations of SHBG showed positive correlations with those of oestradiol and progesterone in specimens taken in the late part of the cycle. In view of the weak relationships between serum SHBG and sex steroid concentrations, and the strong relationships between SHBG, weight and body fat percentage, factors other than steroids have to be considered in the regulation of SHBG levels during puberty.

Adolescent↗

Follicular fluid steroid levels and ovarian steroid secretion in polycystic ovarian disease.

Comparison of the plasma levels of steroids between ovarian and peripheral venous blood in polycystic ovarian disease revealed that polycystic ovaries secreted androstenedione, testosterone, dihydrotestosterone, dehydroepiandrosterone and 17-hydroxyprogesterone significantly more than healthy ovaries at the early follicular phase of the cycle, whereas the levels of estradiol and progesterone did not differ from the control values. Follicular cyst fluid from polycystic ovaries showed significantly higher concentrations of testosterone, androstenedione jand dehydroepiandrosterone and much lower levels of estrone, estradiol, progesterone and 17-hydroxyprogesterone than follicular fluid from healthy preovulatory follicles. Testosterone and estradiol did not, however, show any significant difference when follicles in polycystic ovaries were compared to those in healthy ovaries at early follicular phase of the cycle. According to these findings follicle development in polycystic ovaries is arrested at a stage corresponding to the early follicular phase of the cycle. Increased androgen and 17-hydroxyprogesterone secretion by polycystic ovaries seems to originate mainly from the hyperplastic theca interna cells.

Adult↗

Absence of gonadotropin-induced desensitization of testosterone production in the neonatal rat testis.

The formation of testosterone and some of its precursors (pregnenolone, progesterone, 17-hydroxyprogesterone and androstenedione) was studied in response to hCG stimulation in neonatal (5-day-old) and adult (60-day-old) male rats. Evidence for a biphasic testosterone response was observed at both ages, with a sharp increase within the first hours, and a secondary peak at 2-3 days after the hormone injection, when monitored by intratesticular and serum steroid measurements. The decreased testosterone production between the two peaks coincided in the adult animals with a marked increase of progesterone and 17-hydroxyprogesterone production, in keeping with the known gonadotropin-induced lesions of testicular androgen production. In contrast, no increase in C21-form testosterone precursors could be observed in the neonatal rat. When in vitro testicular production of cAMP, testosterone and progesterone was studied at the two ages 24 h after the hCG injection, a decrease in extracellular cAMP and testosterone but an increase in progesterone was observed in the adult testis. In the neonate, cAMP production was decreased, but testosterone production stayed high, and progesterone production increased only marginally. The present results indicate that the adult-type steroidogenic lesions following in vivo hCG stimulation, resulting in decreased testosterone production and accumulation of C21 steroid precursors, are not operative during the fetal-neonatal growth phase of rat testis Leydig cells.

17-alpha-Hydroxyprogesterone↗

Benign premature adrenarche: clinical features and serum steroid levels.

18 girls with premature adrenarche were evaluated both clinically and by serum steroid measurements. Age at first appearance of the symptoms ranged from 3.0 to 7.8 years. Clinical findings included pubic or axillary hair, acne, accelerated growth, adult-type perspiration and oily skin or hair. Bone age was 0.3-3.2 years ahead of chronological age. 15 of these 18 girls had accelerated growth and most of these already before the appearance of pubic hair. Five girls had severe acne requiring topical treatment. Serum dehydroepiandrosterone was elevated for age in all patients. Androstenedione and testosterone correlated positively with the dehydroepiandrosterone values. Dihydrotestosterone was also elevated in many girls. Administration of dexamethasone brought about a rapid normalization of the elevated steroid levels.

17-alpha-Hydroxyprogesterone↗

Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles.

The associations between age at menarche and the hormonal patterns of adolescent menstrual cycles were investigated to obtain information as to why early menarche is an important risk factor for breast cancer. An initial group of 200 schoolgirls, 7-17 yr old, was investigated longitudinally 3 times at 1.5-yr intervals. A serum progesterone concentration in the latter part of the cycle exceeding 6.4 nmol/liter (2.0 ng/ml) was considered to signify an ovulatory cycle, and a concentration less than 1.6 nmol/liter (0.5 ng/ml) an anovulatory cycle. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche (P less than 0.001 for both variables). Early menarche was associated with early onset of ovulatory cycles. The times from menarche until 50% of the cycles were ovulatory were about 1, 3, and 4.5 yr when the ages at menarche were less than 12.0, 12.0-12.9, and more than or equal to 13.0 yr, respectively. Girls with a menarcheal age below 12.0 yr had higher serum estradiol but lower testosterone and dehydroepiandrosterone concentrations than subjects with later menarche. The estradiol to dehydroepiandrosterone ratio was already higher before menarche in subjects who displayed early menarche during follow-up. These findings show that the increase in adrenal androgen secretion was mainly related to chronological age and was not affected by the time of menarche. The demonstration of early ovulation after early menarche is in conflict with the estrogen-window hypothesis suggesting a longer duration of anovulatory cycles to explain the increased risk of breast cancer after early menarche. Other theories should therefore be considered, among them the following: 1) high serum progesterone concentration in association with normal or high serum estradiol at puberty increases the risk, 2) only the early and relatively high estrogen concentrations are important, or 3) the estrogen to androgen ratio is the critical factor, with androgens having a protective effect.

Adolescent↗

Subnormal pubertal increases of serum androgens in Turner's syndrome.

60 patients (139 blood specimens) with Turner's syndrome were investigated in order to obtain information concerning the origin of the increments of androgens during puberty. The concentrations of serum FSH, LH, estradiol, testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone and pregnenolone in patients less than 10 years old were identical to those previously found in normal healthy girls of the same age. Hence, in adrenarche the early increase of androgen secretion is independent of gonadal hormone secretion. The later increases in serum testosterone and androstenedione in our patients were very small, and the age of 15 years, their concentrations were 50 and 60%, respectively, of the corresponding levels in normal girls of the same age. After 13 years of age, the mean serum dehydroepiandrosterone concentration was also slightly, but significantly (20-30%), lower than in normal girls of the same age. It is concluded that the ovaries are responsible for most of the pubertal rises in circulating testosterone and androstenedione, and possibly for a small part of the late pubertal rise in dehydroepiandrosterone.

Adolescent↗

Steroids in spermatic and peripheral vein blood in testicular feminization.

Steroid secretion by the testes in three postpubertal patients with testicular feminization was studied by comparing the steroid concentrations in spermatic and peripheral blood samples obtained prior to gonadectomy. Testosterone, dehydroepiandrosterone (DHEA), and androstenedione were the predominant steroids secreted by these testes. Values for spermatic vein testosterone (60 to 700 nmoles/liter) were lower than those previously reported for normal men, but values for DHEA (20 to 240 nmoles/liter) and androstenedione (30 to 250 nmoles/liter) were within the range found in normal men. The testes of these three patients also secreted pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, dihydrotestosterone, testosterone sulfate, and estradiol. After gonadectomy, the plasma concentration of estradiol declined considerably less than that of testosterone, indicating that estrogen formation from adrenal precursors continued after gonadectomy in these patients.

Adolescent↗

Serum steroids and pituitary hormones in female puberty: a partly longitudinal study.

Pubertal development of 200 normal girls, 7--17 years of age, was investigated in a partly longitudinal manner with two examinations 1.5 years apart. Samples from postmenarchal girls were taken on days 6--9 and 20--23 of the menstrual cycle. Serum pregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, androsterone, oestradiol and cortisol as well as ACTH, FSH, LH and prolactin were measured radioimmunologically and were related to bone age, breast and pubic hair developmental stages, and gynaecological age. In the samples of premenarchal girls as well as the follicular phase of postmenarchal girls the concentration of all the steroids increased with age. Of all the steroids measured, serum dehydroepiandrosterone and pregnenolone displayed the earlier increase, from the youngest age group of 7.5 years onwards. Serum oestradiol testosterone and androstenedione in creased rapidly from the bone age group of 9.5 years (subjects 9.0--9.9 years of age) onwards, in close association with the appearance of the first physical signs of puberty. A marked increase in these three steroids continued until 13.5 years, the age at which menarche took place. Menarche was followed by a plateau of 1--2 years duration and then a second increase took place up to the two oldest age groups (17.5 and 18.5 years bone age), a trend seen in the follicular phase levels of all the steroids measured. The 5 alpha-dihydrotesterone/testosterone ratio decreased with increasing testosterone concentration. Serum oestradiol, testosterone, androstenedione, dehydroepiandrosterone and FSH showed no overlapping in the 2.5--97.5% range of concentrations and androsterone and LH in the 16--84% range between prepubertal and postmenarchal subjects. Pregnenolone, progesterone, 17-hydroxyprogesterone, 5 alpha-dihydrotesterone, cortisol, ACTH and prolactin overlapped even in the 16--84% range between these two groups of subjects. In postmenarchal girls, about 80% of the cycles were anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. The background of the majority of the anovulatory cycles seems to be a physiological variant of the pattern seen in the polycystic ovary syndrome: the levels of testosterone, and androstenedione and LH were increased in anovulatory cycles compared to ovulatory ones.

Adolescent↗

Serum prolactin, FSH and LH during puberty in girls and boys.

Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.

Adolescent↗

Hormonal pattern of adolescent menstrual cycles.

Serum FSH, LH, PRL, estradiol, pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, and androsterone were measured radioimmunologically in 20 normal girls aged 13-17 yr. Samples were taken every day or every second day during one menstrual cycle. The cycles recorded could be divided into three groups. The first and oldest group consisted of 10 girls with a mean gynecological age (years since menarche) of 2.9 yr. The luteal phase was at least 11 days and the progesterone concentration was at least 5 ng/ml. The testosterone rise (mean, 55%) on the day of LH surge correlated well with the simultaneous progesterone rise (mean, 270%) and the following luteal progesterone secretion. A negative correlation was seen between the FSH concentration on days 3-4 of the cycle and the length of the follicular phase. The second group consisted of 4 girls who had a mean gynecological age of 1.5 yr. The luteal phase was of 4- to 8-day duration and the progesterone secretion was lower than in group I. The follicular phase testosterone concentration was lower in group II as compared to group I. No "periovulatory" testosterone increases were seen, although every cycle displayed an LH and FSH peak. The third group consisted of 6 girls with a mean gynecological age of 1.1 yr. These cycles were anovulatory, as the serum progesterone concentration never exceeded 1.0 ng/ml. In two cycles, signs of follicular maturation were seen. In the four others, the androgen levels tended to be elevated. In two cases, the testosterone and androstenedione concentrations were 2-4 times elevated from the beginning of these two cycles. Thus, the hormonal pattern of adolescent menstrual cycles is far from uniform. It is very likely that in addition to gonadotropins, estradiol and progesterone, androgens may also have a role in the development and maintenance of normal menstrual function in the female.

Adolescent↗

Simultaneous determination of five sex hormones in human serum by radioimmunoassay after chromatography on Lipidex-5000.

We describe a method for determination of pregnenolone, progesterone, 17alpha-hydroxyprogesterone, testosterone, and 5alpha-dihydrotestosterone in 1-2 ml of serum from male or female. Using microcolumns of Lipidex-5000 (hydroxyalkoxypropyl Sephadex, 0.5 g) and light petroleum/chloroform (97/3) as the solvent during chromatography, we resolved these five steroids into four fractions, with pregnenolone and 5alpha-dihydrotestosterone eluting together. By use of selected antibodies, the latter two steroids were also determined specifically. Use of microcolumns allowed minimization of solvent volumes and sample transfers. Consequently, blank values for all the five steroids were negligible. Lowest measureable concentrations (in ng/liter) were: pregnenolone 100, progesterone 25, 17alpha-hydroxyprogesterone 50, testosterone 25, and 5alpha-dihydrotestosterone 25. Intra-assay and inter-assay coefficients of variation ranged from 5 to 9% and 10 to 15%, respectively, for the five steroids. Serum concentrations of these steroids are given for women in the follicular and luteal phases of the menstrual cycle and for women on oral contraceptives of the combination type, as well as for normal men.

Antibody Specificity↗

Lipidex chromatography in the radioimmunoassay of serum and urinary cortisol.

A highly specific method for the determination of cortisol in human serum and urine is described. The sample is first extracted with diethyl ether/ethyl acetate (1 : 1, by vol.), then chromatographed on a highly lipophilic derivative of Sephadex (hydroxyalkoxypropyl Sephadex, Lipidex) in light petroleum/chloroform (1 : 1, by vol.), and finally cortisol is measured by radioimmunoassay using a cortisol-21-BSA antiserum. Bound and unbound radioactivities are separated using dextran-coated charcoal technique. The 8 a.m. values (mean +/- S.D.) of cortisol among 11 young females and 16 young males were 152 +/- 32 ng/ml (range 111-235) and 185 +/- 21 ng/ml (103-232), respectively. The respective values at 4 p.m. were 84 +/- 29 ng/ml (26-117) and 84 +/- 36 ng/ml (32-172). The importance of Lipidex chromatography was demonstrated with assays of serum samples from children with congenital adrenal hyperplasia; without chromatography cortisol values were 6 times those with chromatography. Specific cortisol assays from pregnancy serum also necessitated Lipidex chromatography. Among 11 young men and 9 young women the mean daily urinary cortisol excretion was 56 +/- 26 mug (32-109) and 60 +/- 24 mug (39-109), respectively. Specific urinary cortisol determination could not be achieved without Lipidex chromatography.

Adrenal Glands↗