Serum Steroid Concentrations Research Articles

Changes in serum concentrations of steroid hormones, thyroxine, and vitellogenin during spawning migration of the chum slamon, Oncorhynchus keta

Changes in serum concentrations of various steroid hormones (estradiol-17β, androgens, 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-diOHprog)), thyroxine and vitellogenin during the spawning migration (from the coastal sea to the spawning ground) of male and female chum salmon ( Oncorhynchus keta) were investigated. In females, estradiol-17β levels were high during the early phases of the migration (sea and prespawning period), but significantly decreased in fish at the time of the spawning period (oocyte maturation and ovulation). The changes in estradiol-17β levels coincided with those of serum vitellogenin levels. High levels of androgens were observed throughout the sampling period. Serum 17α,20β-diOHprog levels were extremely low during the early phases of spawning migration, but elevated dramatically in mature or ovulating females. In males, serum concentrations of androgens were high during the early phases of the migration, but sharply declined around the time of the spawning period (spermiation). Similar to females during final maturation, the serum levels of 17α,20β-diOHprog in males rapidly increased during spermiation, although the magnitude of the elevation in males was smaller than in females. Serum thyroxine levels were highest both in females and males collected in the coastal sea, and the levels decreased during the spawning migration. These findings are discussed in relation to anadromous migration and sexual maturation of chum salmon.

Steroidogenic responsiveness of the monkey corpus luteum to exogenous chorionic gonadotropin.

Groups of female rhesus monkeys were given a 5-day regimen of im injections of hCG (30, 60, 90, 180, and 360 IU, respectively) beginning 2, 6, 10, or 14 days after the midcycle LH surge (day 0). Serum progesterone concentrations in the day 2 treatment group did not differ markedly from values observed in control monkeys throughout normal menstrual cycles. In contrast, monkeys receiving hCG beginning on days 6, 10 or 14 had immediate significant increases in serum progesterone in response to the first injection of hCG. Dramatic responses were seen in the day 6 and 10 groups (2.5- and 5-fold elevations in serum progesterone, respectively); progesterone values plateaued at about 13 ng/ml during the hCG treatment interval. Monkeys receiving hCG on day 14 had 4-fold elevations in serum progesterone, but concentrations did not exceed 6 ng/ml. Serum estradiol increased significantly after hCG to concentrations between 200-300 pg/ml in all treatment groups; peak values were seen at the time of or in the days immediately after the last hCG injection. Serum testosterone concentrations were not significantly altered by hCG administration at any stage of the luteal phase. hCG did not sustain serum steroid hormone concentrations in monkeys with the corpus luteum removed on day 10 of the luteal phase. A 10-day regimen of increasing hCG doses beginning on day 10 of the luteal phase mimicked the steroid hormone secretion patterns observed in control monkeys during early pregnancy. The data show that the qualitative and quantitative steroidogenic capacities of monkey corpora lutea after a gonadotropin challenge are profoundly affected by luteal age.

Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep.

The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40-60 min) and had elevated LH levels (16.1 +/- 1.6 ng/ml; mean +/- SE) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo

The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th–12th week of gestation) was investigated in volunteers; control group ( n = 11), AG group [1000 mg AG orally at test begin ( n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 15% ( x SD) ( n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 17% ( x SD) ( n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

Metabolism of injectable formulations of contraceptive steroids in obese and thin women

Blood levels of the injectable contraceptives DepoProvera and Norigest were studied in groups of obese and thin women. From an analysis of the straight lines obtained by plotting the logarithm of the serum steroid concentration against time after injection, there was no difference between the obese and thin women in the blood levels of the contraceptive steroids nor was there any difference in the rate of return of ovarian follicular and luteal function.

Transfer of contraceptive steroids in milk of women using long-acting gestagens

Levels of norethisterone and medroxyprogesterone acetate were measured in serum and milk of women receiving the injectable contraceptive formulations Norigest and DepoProvera, respectively, throughout complete injection intervals. In 5 of 10 women receiving Norigest, serum norethisterone levels were undetectable by 8 weeks after injection and only 2 women had detectable levels of norethisterone in milk at this time. In contrast, 8 of 10 women receiving DepoProvera had detectable levels of medroxyprogesterone acetate in both serum and milk 12 weeks after injection. The ratio of the milk:serum concentrations of norethisterone varied from 0.12 to 0.92 (mean 0.34) and for medroxyprogesterone acetate from 0.12 to 2.60 (mean 0.88). It is unlikely that these differences between the two formulations are due entirely to differences between the binding of norethisterone and medroxyprogesterone acetate to serum proteins. The area under the curve of serum steroid concentrations plotted against time was only 50% higher for women injected with DepoProvera than for those injected with Norigest but the area under the curve for milk values was 400 times higher. Assuming the infant ingests 600 ml milk daily, the daily intake of steroids in the first week after injection would be 0.5 to 2.4 μg for norethisterone and 1 to 13 μg for medroxyprogesterone acetate. By 8 weeks after injection, the amount of norethisterone ingested would be small but that of medroxyprogesterone acetate would still be significant.

Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon.

Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 X 10(6) units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERC and ERN, respectively) and progestin receptors (PRC and PRN) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERC, ERN, PRC and PRN affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.

Urinary and serum steroid concentrations in the management of congenital adrenal hyperplasia. Lack of physiologic correlations.

Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, testosterone, and androstenedione and 24-hour excretion of 17-ketosteroids and pregnanetriol were measured serially in 18 children with congenital adrenal hyperplasia (21-hydroxylase deficiency) during a two-year period. Correlations were sought between results of measurements of these steroids and clinical progress assessed by physical examination and skeletal maturity to determine if measurement of concentration of these substances at a single point in time could be used to gauge the dose of corticosteroids for optimum treatment. We found that these measurements of steroids were generally not useful indicators of optimum control of the disease. Repeated careful clinical examination and assessment of changes in growth velocity and skeletal maturation seem to be the best criteria on which to base dosage of corticosteroids used for therapy.

Luteal Function in Baboons with Administration of the Antiestrogen Ethamoxytriphetol (MER-25) Throughout the Luteal Phase of the Menstrual Cycle1

Administration of the antiestrogen ethamoxytriphetol (MER-25) during late baboon gestation has been reported to result in a marked decline in progesterone (P) production rate. Since both the placenta and corpus luteum appear to secrete P during late baboon gestation, this decline in P may reflect a loss in luteal and/or placental function. Therefore, the present study determined the effect of administration of the antiestrogen MER-25 upon serum steroid concentrations during the luteal phase of the baboon menstrual cycle, a tijne when the source of P is almost exclusively the corpus luteum, Six baboons were bled throughout a control menstrual cycle and during daily administration (15 mg/kg BW, p.o.) of MER25 throughout the luteal phase of the following cycle. Mean (± SEM) length of the luteal phase of the menstrual cycle was the same in baboons with no treatment (18 ± 0 days) and after MER-25 administration (18 ± 0 days). Mean (± SEM) serum concentrations of P were similar in the luteal phase with no treatment (5.2 ± 0.7 ng/ml) and during MER-25 administration (5.0 ± 0.6 ng/ml). Serum P attained similar peak values of concentration in the luteal phase before and after antiestrogen administration and was detectable in the serum for a similar duration of the lutes] phase of both cycles. Mean (± SEM) serum concentrations of 17-hydroxyprogesterone (17-01(P), which may also provide an index of lutes] function, were similar in the luteal phase of the menstrual cycle in baboons with no treatment (0.53 ± 0.20 nglml) and during administration of MER-25 (0.42 ± 0.15 ng/inl). Serum estradiol (E2) concentrations attained a peak at midcycle, then declined to low values, and MER-25 had no effect upon serum E2.

Endocrine profiles and fertility status of human menstrual cycles of varying follicular phase length

Assessment of the relationship between ovarian endocrine function and follicular phase length was made in 48 patients (51 cycles) with spontaneous ovular cycles of varying length. On the basis of follicular phase length when measured from the first day of menstruation to, and including, the day of the luteinizing hormone (LH) peak, cycles were grouped into short (less than 21 days), medium (12 to 16 days), and long (more than 6 days). Daily serum LH, androstenedione, 17 beta-estradiol, progesterone, and 17 alpha-hydroxyprogesterone concentrations were determined in the periovular period. The overall pattern of serum steroid concentrations in medium and long cycles was similar to that previously described for normal women. However, cycles with a short follicular phase had lower mean concentrations of androstenedione and estradiol. In order to assess the fertility potential of cycles with follicular phases of varying length, the prior 265 cycles of 92 consecutive patients who conceived with artificial insemination by donor (AID) were studied. In all cases, insemination occurred on day 0 and day + 1 with respect to the LH peak, and all cycles were assumed to have equal fertility potential. Statistical analysis revealed no significant difference in fertility potential among cycles with follicular phases of differing length.

Induction of superovulation in the cyclic hamster by a single injection of antiluteinizing hormone serum.

Interruption of pregnancy in the hamster with equine antibovine LH (anti-LH) induces superovulation of about 30 ova at the subsequent estrus. In view of the different hormonal profiles and antral follicular development in pregnant and cyclic hamsters, the present experiments were designed to ascertain the effects of anti-LH on the serum concentrations of steroids, ovarian follicular development, and ovulation in the cyclic hamster. Hamsters injected sc on the morning of ovulation (day 1 of cycle) with 100 μl anti-LH spontaneously ovulated 31.5 eggs at the next ovulation instead of the normal number of 13 ova. The normal 4-day cycle was lengthened to 5 days after anti-LH, but subsequent cycles reverted to 4 days, and the normal number of ova was shed. Anti-LH on day 1 did not affect serum progesterone levels on day 2, but serum estradiol was depressed until day 4, whereas in the normal hamster, estradiol increases on day 3. When anti-LH was given on day 4 (proestrus), the hamsters ovulated the next day an average of 11 ova, but in the subsequent cycle (5–6 days), the mean number of ovulations was 29. Thus, anti-LH induces superovulation when injected in the periovulatory period (days 4 and 1) when serum FSH levels are high. A quantitative study of follicular development after the injection of anti-LH at 0900 h on day 1 revealed that for 12 h afterwards, follicular development was unaffected. However, by day 2, a wave of atresia destroyed the larger preantral follicles. On day 3, the ovary was repopulated with large preantral follicles, and this was followed by a greater than normal number of antral and intermediate sized follicles, thus culminating in superovulation. (Endocrinology108: 1903, 1981)

Clinical response to metyrapone as indicated by measurement of mineralocorticoids and glucocorticoids in normal children.

The effect of 24-h metyrapone administration on adrenal mineralocorticoid and glucocorticoid pathways has been studied in normal children. Urine and serum steroid concentrations were evaluated. Simultaneous determinations of deoxycorticosterone (DOC), corticosterone (B), cortisol (F), and aldosterone (aldo), in both urine and serum, were carried out by celite column chromatography and radioimmunoassay. 11-deoxycortisol (Compound S) in serum and urine, urinary free 18-hydroxydeoxycorticosterone (18-OH-DOC), urinary free 18-hydroxycorticosterone (18-OH-B), and urinary aldosterone-18-glucuronide (pH 1 aldo) were measured separately by specific methods. Conclusions drawn were that (1) Useful indices of metyrapone effect were the marked rise of 11-deoxysteroids (DOC and S), and the fall of aldo and 18-OH-B; no changes occurred in 18-OH-DOC and the 11-hydroxylated steroids (B, F); (2) Serum and urine values were significantly correlated, indicating that both were equally reliable in the evaluation of the metyrapone test; (3) Hormonal ratios indicate that metyrapone inhibition affected the 11-hydroxylation of DOC and Compound S, and the 18-hydroxylation of DOC and B; and (4) The correlation between DOC/B and S/F ratios was highly significant (r = 0.86; P less than 0.0001), showing the same degree of inhibition of 11-hydroxylase functions for both 17-hydroxy (17-OHS) and 17-deoxysteroids.

LH-induced testicular steroid secretion after FSH treatment in immature and young adult hypophysectomized rats.

Immature and young adult male rats were hypophysectomized on day 21 and 71 respectively. Beginning 2 days later, animals received five daily subcutaneous injections of 4 microgram/100 g body weight of NIAMDD-oFSH-13 or saline. On the sixth day the rats received either 15 microgram/100 g body weight of NIAMDD-oLH-21 or saline intraperitoneally and were decapitated 1 hr later. Serum levels of steroids were measured by radioimmunoassay. Serum steroid levels in animals receiving a saline injection on day 6 were low to undetectable and not affected by pretreatment. The serum steroid concentrations after LH challenge on day 6 were altered by FSH pretreatment. In immature rats, pretreatment with FSH resulted in a significant increase in 17 hydroxyprogesterone, androstenedione and testosterone. Progesterone and estradiol were unaffected, while 5 alpha dihydrotestosterone was elevated but not significantly. In young adults, FSH pretreatment resulted in increased levels of androstenedione, testosterone, and 5 alpha dihydrotestosterone, but not progesterone, 17 hydroxyprogesterone, or estradiol. These data suggest that FSH may play a role in stimulating cholesterol side chain cleavage activity, the 17 alpha hydroxylase, the C17-C20 lyase as well as the 17 beta hydroxysteroid dehydrogenase at puberty. Additionally, FSH may be involved in the maintenance of cholesterol side chain cleavage activity, the C17-C20 lyase and the 17 beta hydroxysteroid dehydrogenase in the adult rat.

Effects of phenobarbital-induced ovulatory delay on the follicular population and serum levels of steroids and gonadotropins in the hamster: A model for atresia.

A model was developed for the study of atresia of preovulatory follicles in the hamster. The effects of ovulatory delay on the ovarian follicular population, number of ova spontaneously ovulated, and serum concentrations of steroids and gonadotropins were assessed. This model was based on earlier observations of Everett and Sawyer (1950) who reported atresia of rat preovulatory follicles after 3 or 4 days of continued postponement of ovulation with sodium pentobarbital. Cyclic hamsters weighing 90-110 g were maintained on a 14L:1OD schedule (lights on at 0500 h). Ilamsters injected s.c. with 6.5 mg phenobarbital (Phen)/100 g BW at 1300 h on proestrus exhibited 1 day of ovulatory delay. Hamsters injected with 6.5 mg Phen at 1300 h on proestrus and also with 13 mg Phen at 1200 h the next day, exhibited a 2-day delay;an additional injection of 19.5 mg Phen at 1200 h on the following day was required for 3 days of ovulatory delay. Histological examination of the ovary revealed that the diameter of antral follicles on proestrus (561 ± 12pm) increased significantly after 1 day of ovulatory delay (680 ± 11 pm). After 2 days of ovulatory delay, no significant alteration of antral follicular diameter was observed; however, on Day 3 of ovulatory delay, the original set of preovulatory follicles exhibited early signs of atresia as evidenced by degenerating granulosa cells and by pyknotic nuclei within the oocytes. Interestingly, on Day 3 of delay a new set of small-diameter antral follicles (527 ± 22 pm) was observed, indicating that as the original set of preovulatory follicles became atretic they were gradually replaced by a new set of antral follicles. Unlike the rat after 3 days of barbiturate administration, the hamster ovulated 1.5 days later. This was due to the rapid recruitment of antral follicles as the original set became atretic. The number of ova shed after 2 (17.9 ± 0.4 ova) and 3 (19.1 ± 0.6 ova) days of delay (but not after 1-day delay, 12.5 ± 0.3 ova) was significantly higher than in untreated cyclic hamsters (11.3 ± 0.7 ova). The higher ovulation rate may have been the result of recruitment of stage V follicles observed only in delayed hamsters. Injections of Phen were required at 1200 h (1 hearlier tban the first injection) to cause 2 and 3

SERUM PREGNENOLONE, PROGESTERONE, 17α‐HYDROXYPROGESTERONE, ANDROSTENEDIONE, TESTOSTERONE, 5α‐DIHYDROTESTOSTERONE AND ANDROSTERONE DURING PUBERTY IN BOYS

SUMMARYWe have determined the concentrations of pregnenolone, progesterone, 17α‐hydroxyprogesterone, androstenedione, testosterone, 5α‐dihydrotestosler‐one and androsterone in serum samples collected from a total of seventy‐nine boys who were 8–18 years of age at the time the first blood samples were drawn. Additional samples were drawn from sixty‐six and forty‐four of these boys after 1 and 2 year intervals, respectively. The first increases in serum steroid concentrations were those of androstenedione and androsterone, thus supporting the hypothesis that an early activation of the adrenal cortex is the first hormonal change in puberty. This increase in serum androstenedione occurred 2 years earlier than the first significant increase in serum testosterone, which took place by 13 5 years, after the first signs of external genital development, but in concert with the onset of pubic hair growth. The serum concentrations of 5α‐dihydrotestosterone were closely related to those of testosterone, but the relative increases were smaller, the consequence of which is a decrease in the ratio of 5α‐dihydrotestosterone: testosterone throughout puberty. The main increase in serum androsterone tends to take place after that of 5α‐dihydrotestosterone and testosterone. In comparison with the four androgens, the serum concentrations of their C21 precursors correlated rather poorly with the physical signs of advancing puberty. As in the case of androstenedione, the concentrations of pregnenolone and 17α‐hydroxyprogesterone were relatively high in the youngest age groups, which probably also reflects an early adrenal activation. In contrast to testosterone, the major increases in precursor steroids occur at a relatively late stage of puberty. It seems likely therefore that a major qualitative shift in the testicular secretion of steroids occurs during puberty in boys.

Changes in follicular fluid and serum concentrations of steroids in PMS treated immature rats following LH administration.

The effect of an ovulatory dose (10 �ng/rat) of luteinizing hormone (NIH-LH-B8) on follicular fluid (FF) and peripheral serum concentrations of steroids in pregnant mare’s serum (PMS) treated rats (4 lU/rat) was studied over a 10 h period. Within I h of LH administration, FF and serum concentrations of progesterone (P) had risen 7- and 10-fold, respectively, the concentrations remaining elevated for the remalnder of the experiment. In contrast, the FF and serum concentrations of androgen (A) and estradiol-17�3 (E) after rising only slightly over the first 1-2 h after LH administration, steadily declined thereafter to reach extremely low levels by 10 h. These findings not only show the range in concentrations of rat FF steroids but also demonstrate that approaching ovulation in the rat is associated with a change in follicular steroidogenesis with P production being stimulated while A and E production is suppressed. In addition, these findings indicate that the measurement of FF steroids is a useful means of assessingthe steroidogenic activity of the follicle.

Management of Congenital Adrenal Hyperplasia Using Serum Dehydroepiandrosterone Sulfate and 17-Hydroxyprogesterone Concentrations

Simultaneous serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) were compared with urinary 17-ketosteroid (17-KS) and pregnanetriol (PT) excretion during therapy in 18 prepubertal patients with the 21-hydroxylase deficiency form of congenital adrenal hyperplasia (CAH). Patients were classified into those in good, poor, or questionable control on the basis of clinical examination, skeletal age, and 17-KS and PT excretion. During therapy, use of serum steroid concentrations was found to be nearly as accurate in judging adequacy of control as use of urine steroid concentrations. Of 34 evaluations, a definite assessment of adequacy of control could be arrived at 25 times using urinary values and 22 times using both serum DHEA-S and 17-OHP concentrations. DHEA-S concentration responded sluggishly when treatment was not adequate, being greater than 100 microgram/dl only in patients significantly undertreated. It was never elevated in well-controlled patients. Mid-afternoon 17-OHP concentrations were less than 200 ng/dl in well-controlled patients but readily escaped suppression and could not be used to differentiate poor from borderline control or from temporary noncompliance. Therefore, an increases DHEA-S concentration indicated poor control and a suppressed 17-OHP concentration indicated good control. The combination of normal DHEA-S level with elevated 17-OHP level, however, did not permit exact evaluation of the degree of control. Of significance is that not all patients with CAH present with an elevated DHEA-S concentration, and only in those in whom an elevated level has been documented can DHEA-S level be used as an index of control during therapy.

Simultaneous determination of eight adrenal steroids in human serum by radioimmunoassay

A radioimmunological method for estimation of progesterone, 17-OH-progesterone, deoxycorticosterone (DOC), corticosterone, 11-deoxycortisol, 18-OH-deoxycorticosterone (18-OH-DOC), aldosterone and cortisol in one sample of human serum is described. The procedure involves separation of the steroids into four fractions by liquid-liquid partition, purification by paper chromatography and quantitation by radioimmunoassay. The parameters precision, accuracy, sensitivity and specificity of the present method are shown to be equivalent to those of single steroid radioimmunoassays. Mean serum concentrations in a series of normal males were as follows : progesterone, 17.9 ng/100 ml ; 17-OH-progesterone, 179 ng/100 ml; DOC, 6.6 ng/100 ml; corticosterone, 421 ng/100 ml; 11-deoxycortisol, 49 ng/100 ml; 18-OH-DOC, 20 ng/100 ml; aldosterone, 12.4 ng/100 ml and cortisol, 14.4 μg/100 ml. The percentage increment of steroid serum concentration after adrenocortical stimulation by ACTH or insulin induced hypoglycemia differed markedly between the individual steroids. The changes of serum steroid concentrations after oral administration of metyrapone are shown. Angiotensin II infusion caused a significant increase of serum aldosterone and a significant fall of serum cortisol, while serum concentrations of the other steroids remained unaltered.

Effects of active immunisation against steroids upon circulating hormone concentrations

Male and female Sprague-Dawley rats were actively immunised against testosterone-3-(O-carboxymethyl)oximino-bovine serum albumin (T-3-BSA) or oestradiol(17β)-6-(O-carboxymethyl)oximino-BSA(E 2-6-BSA). Animals were test bled at monthly intervals under ether anaesthesia from the jugular vein. Serum was used for hormone analysis by radioimmunoassay throughout. The common finding was that the presence of antisteroid antibodies was accompanied by total serum steroid concentrations showing 100–1000 fold increase over control values. In the male, immunisation against T-3-BSA was also accompanied by elevated LH and FSH, and histological examination of the reproductive tract revealed marked Leydig cell hyperplasia but a reduction in the size of the ventral prostate. The picture in the serum from female rats resembled that from the male except that LH values did not rise. Persistent vaginal cornification was observed and the ovaries had large fluid-filled cysts although no granulosa cells could be seen lining the cysts, and corpora lutea were absent. In both sexes the ‘free’ circulating testosterone concentration fell over the period of immunisation but neither showed any change in serum prolactin levels. Animals immunised against E 2-6-BSA showed certain similarities with the above group in that serum antibody titres rose to the accompaniment of elevated total oestradiol(17β) concentrations but LH was raised only in the females and neither sex showed any differences in FSH or prolactin levels. In the male, testosterone concentrations were significantly above controls in the intermediate stages of immunisation but no pathological changes were observed in the reproductive tract on sacrifice. The vaginal and ovarian picture in the female was similar to that described above although the cysts were rather smaller in size. Both sexes appeared to have slightly raised concentrations of ‘free’ E 2.

Serum 17-α-hydroxyprogesterone, progesterone, estradiol, and testosterone in the diagnosis and management of congenital adrenal hyperplasia

The value of determining concentrations of serum 17-α-hydroxyprogesterone, progesterone, estradiol, and testosterone in the diagnosis and management of congenital adrenal hyperplasia was studied. The values recorded were compared with established criteria of control: growth rate, advancement of bone age, degree of virilization, and 24-hour urine excretion of 17-ketosteroids and pregnanetriol. Serum 17-OHP concentrations were diagnostic in five new patients with CAH; they ranged from 100–312 ng/ml (50 to 450-fold above normal); serum progesterone concentrations ranged from 7–24 ng/ml (2 to 50-fold above normal). In the long-term management no one serum steroid concentration alone could be relied upon to determine adequacy of control. It appears that several variables, including diurnal variation, timing of the sample in relation to the last dose of a glucocorticoid, and chronic suppression of the hypothalamic-pituitary-adrenal axis, in addition to the degree of control, may affect a single serum steroid determination. When an acceptable range of normal in CAH for concentration of serum 17-OPH was broadened to 4 ng/ml and for progesterone to 1 ng/ml, there was a fairly good correlation of serum steroid concentrations with degree of control.