F. Facchinetti

β-LIPOTROPHIN AND β-ENDORPHIN PLASMA LEVELS DURING PREGNANCY

β‐lipotrophin (β‐LPH) and β‐endorphin (β‐EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G‐75 column chromatography in plasma samples from controls (ten healthy males and twenty‐six young women in early follicular phase), from eighty‐two pregnant women in weeks 9–40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in β‐LPH (120·6 ± 8·5 pg/ml) or β‐EP (31·1 ± 2·4 pg/ml) plasma levels or in their molar ratio (1·34 ± 0·09) (MR). β‐LPH plasma levels increased in early pregnancy (13–16 weeks) (185·0 ± 27·1 pg/ml) and remained high until weeks 21–24, then declining to levels similar to those of controls. β‐EP plasma levels were significantly depressed in weeks 9–12 (20·7 ± 5·3 pg/ml), subsequently increasing to a maximum at weeks 36–37 (42·7 ± 6·8 pg/ml). β‐LPH/β‐EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that β‐LPH and β‐EP present different patterns throughout pregnancy and that β‐EP levels increase progressively, reaching the highest concentrations at term. At delivery, both β‐LPH and β‐EP showed maximum values (β‐LPH: 230·2 ± 20·4 pg/ml; β‐EP: 78·0 ± 7·4 pg/ml) and a MR of 1·02 ± 0·10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in β‐LPH and β‐EP plasma levels. Cord blood specimens showed a wide range of values (β‐LPH:75–347 pg/ml; β‐EP: 16–287 pg/ml) with a MR of 1·21 ± 0·14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by β‐LPH levels of 119·4 ± 26·4 pg/ml and β‐EP levels of 29·6 ± 7·5 pg/ml.

ADRENAL AND GONADAL STEROIDS IN GIRLS DURING SEXUAL MATURATION

The peripheral venous plasma concentrations of gonadotrophins (LH and FSH), prolactin (Prl), cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone‐sulphate (DHA‐S), pregnenolone (Δ5P), progesterone (P), 17‐hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were measured in girls at different stages of sexual development (from P1 to P4–5 according to Tanner, 1962). Both gonadotrophins increase progressively during sexual maturation, to reach the highest concentrations in P4–5. However, the FSH values were significantly lower in these P4–5 pre‐menarchal girls than those found in adult women in the early follicular phase. No significant changes were found in plasma Prl, cortisol and 17P levels during pubertal development; in contrast, plasma concentrations of DHA tripled from P1 to P4–5, reaching adult levels. A progressive rise was also found in DHA‐S plasma levels. A significant, but less evident increase was found in Δ5P and P plasma concentrations, from group P1 to P4–5. A, T and DHT levels rose progressively and significantly from P1–2 to the end of sexual maturation. In the case of E2, only a moderate increase was found during pubertal development.

Betalipotropin and betaendorphin in physiological and surgical menopause

Abstractβ-lipotropin (β-LPH) and β-endorphin (β-EP) plasma levels were characterized by a significant decrease in postmenopausal females (22 subjects aged from 56 to 70 yr) when compared to fertile women (22 subjects from 31 to 45 yr). On the contrary, ACTH plasma levels determined in 10 of the premenopausal and 13 of the postmenopausal subjects reported above showed constant levels in both groups. A significant increase in the β-LPH/β-EP molar ratio was observed in postmenopausal females. The plasma β-LPH and β-EP levels, studied before and 6 months after ovariectomy, showed a significant decrease in 8 out of 10 patients, while they remained constant in the other 2. Two subjects, in whom postsurgical samples were taken during a flushing episode, showed β-LPH and β-EP plasma levels which were both higher than the corresponding preovariectomy values. The results suggest that these changes may be important in explaining modifications in behavior and mood frequently found in postmenopausal females and in patients undergoing surgical castration in the fertile age.

Correlations between plasma levels of opioid peptides and adrenal androgens in prepuberty and puberty.

In 139 prepubertal children and in 38 pubertal adolescents plasma levels of ACTH, cortisol, beta-lipotropin (BLPH), beta-endorphin (BEP) and dehydroepiandrosterone sulphate (DHAS) were determined by specific radioimmunoassays directly (steroids) or after plasma purification (peptides). ACTH and cortisol concentrations remain stable during both prepuberty and puberty, while DHAS levels constantly increased from 5 to 16 years. Both BLPH and BEP increase from early infancy to late prepuberty when they reach adult values. During puberty both opioids remain constantly within the adult range. BLPH and BEP concentrations were significantly correlated to those of DHAS throughout prepuberty. These data suggest a possible role of BLPH and BEP in and/or other proopiocortin-related peptides in the development of adrenarche, while the lack of particular changes in these peptide levels during sexual maturation seems to exclude their role in gonadarche and pubertal development.

Changes throughout puberty in adrenal secretion after acth

Abstract After short DXM suppression an i.v. stimulation of 1 U ACTH 1−24 /m 2 b.s. was given to 24 girls aged from 10–13 years, subdivided into groups according to sexual maturation, and to 6 adult female controls. In the samples collected before and after ACTH stimulation, pregnenolone (Δ 5 P), 17α-hydroxyprogesterone (17P), cortisol (F), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), androstenedione (A), testosterone (T) and oestradiol (E 2 ) were measured by radioimmunoassay. The results indicated the efficacy of DXM in inhibiting adrenal steroid secretion in all age groups. While the DXM suppressed values of F were the same in all subjects, significant differences were found in DHA and A which progressively increased according to sexual development.In adult subjects, the basal DXM suppression values of 17P, T and E 2 were significantly higher than in pubertal subjects, confirming the notable ovarian origin of these steroids in adults. After ACTH an important discrepancy was noted between similar F levels in all groups and progressively increasing DHA and A levels with increasing sexual maturation. These results confirm the role of ACTH as stimulator of adrenal cell secretion, but indicate that another factor may be responsible for the development of the adrenal androgen cells during sexual maturation.

Effect of short dexamethasone suppression on plasma steroids in prepubertal and pubertal girls

In 40 girls aged from 2 to 14 years, subdivided into groups according to age and pubertal development, and in 6 adult female volunteers, plasma Cortisol (F), pregnenolone (δ5), de-hydroepiandrosterone (DHA), progesterone (P), 17-hydroxyprogesterone (17P), androstenedi-one (A), testosterone (T) and estradiol (E2) were measured before and after short dexamethasone (DXM) suppression. The results confirmed the capacity of DXM to inhibit plasma steroids in all age groups, except T in 2–9 year old and P1 Tanner’s stage girls. The percentage suppression of each given steroid was constant over the age groups from 6–9 years to P4–5 Tanner’s stage, while lower suppression was found in 17P, P and DHA in 2–5 year old girls and in 17P, DHA and E2 in adult women. These results emphasize thefundamental role of ACTH as the overall stimulating factor of adrenal steroidogenesis but do not negate the possibility of another factor responsible for the development of the adrenal androgen secreting cells throughout prepuberty and puberty.

Adrenal and gonadal steroids and pituitary response to LHRH in girls. I. Delayed puberty

Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone (DHA), dehydroepiandrosterone-sulphate (DHA-S), 17-hydroxyprogesterone (17P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) were measured in basal conditions in eleven young women from 16 to 25 years of age characterized by delayed puberty. The gonadotropin response to LHRH (50μ iv) was also tested in these cases. The results, as far as gonadotropins and E2 are concerned, indicate that delayed puberty in girls is a heterogeneous disorder: an impairment in the negative feedback between E2 and FSH coexists with a reduced ovarian response to endogenous gonadotropins. All cases showed evidence of a more or less pronounced delayed adrenarche, which was demonstrated by the markedly reduced levels of DHA-S and DHA (with the exception of this latter steroid in two cases with idiopathic hirsutism). Furthermore, the very low plasma progesterone (P) levels in all cases suggest the existence of impaired Δ5 — Δ4 isomerase activity in the adrenal cells. Despite the low levels of A and T, DHT is within the upper limits of the normal range in all cases.