Adrenal and gonadal contribution to circulating androgens in spotted hyaenas (Crocuta crocuta) as revealed by LHRH, hCG and ACTH stimulation

Single venous blood samples were collected from 52 hyaenas and serial samples via indwelling jugular catheters from 8 hyaenas. Social status of the hyaenas was unknown. Radioimmunoassay estimations were specific for testosterone, androstenedione, cortisol and LH. No significant differences could be found between the sexes for concentrations of testosterone (adult males 2.9 +/- 1.3 nmol/l; adult females (non-pregnant) 1.6 +/- 0.3 nmol/l). Androstenedione concentrations in sub-adult males were significantly lower than those in females (2.3 +/- 0.05 and 5.5 +/- 1.2 nmol/l). Testosterone and androstenedione concentrations were significantly higher in parous pregnant than in parous non-pregnant females (4.3 +/- 1.4 and 1.6 +/- 0.3; and 23.7 +/- 11.6 and 6.7 +/- 0.9 nmol/l respectively). Both LHRH and hCG elicited elevated androgen concentrations in females in different reproductive categories. Androgens are produced by the ovary in the absence of follicular or luteal structures, indicating androgen production by the interstitial tissue of the ovarian stroma.     

Regulation of plasma sex-steroid-binding protein in adult cynomolgus monkeys (Macaca fascicularis) during different reproductive states

Levels of the sex-steroid binding protein (mSBP) have been characterized in Cynomolgus monkeys, during different stages of reproduction and under hormonal treatments, by an immunoassay allowing a specific and accurate measurement of the protein itself. Using an antiserum specific for native human SBP, we have determined the mSBP level by electroimmunodiffusion. This method correlates closely with the binding capacity measured by a steady-state polyacrylamide electrophoresis. The levels are lower in males (M = 88 +/- 8.6 nmoles/1, n = 6) than in females in the follicular phase (M = 123 +/- 4.4 nmoles/1, n = 5, p less than 0.001) and in castrated males (M = 172 +/- 13.3 nmoles/1, n = 3, p less than 0.001). During gestation, the SBP level decreases (M = 69 +/- 16.3 nmoles/1, n = 7, in the latter part of pregnancy), but during lactation, it is similar to follicular values. Estrogen treatment fails to increase SBP levels in castrated animals, but the values are reduced by testosterone treatment. Since these results are different from those observed in women, we question the validity of using monkeys as models for understanding the mechanisms controlling the concentration of SBP in human blood.     

Feedback regulation of gonadotropic hormone secretion in neonatal pigs

The effect of castration and of administration of charcoal-treated porcine follicular fluid (pFF) containing inhibin-like activity on plasma concentration of gonadotropic hormones was studied in neonatal pigs. Plasma follicle-stimulating hormone (FSH) concentration averaged 25.1 +/- 1.5 ng/ml (mean +/- SEM) in 1-wk-old females and gradually declined to 20.2 +/- 0.7 ng/ml 6 wk later. Ovariectomy did not significantly influence plasma FSH concentration. In males, concentration averaged 8.0 +/- 0.7 ng/ml before castration but rose significantly within 2 days after castration. Injection of luteinizing hormone-releasing hormone (LHRH) did not influence plasma FSH concentrations in intact males, but did in females and in 7-wk-old males castrated at 1 wk. Plasma luteinizing hormone (LH) concentrations in 1-wk-old females (2.2 +/- 0.4 ng/ml) gradually declined and were not influenced by castration. Concentrations of plasma LH in 1-wk-old male piglets (2.8 +/- 0.7 ng/ml) were not significantly influenced by castration within 2 days but were significantly higher 6 wk later. LHRH induced a significant rise in plasma LH concentrations in all animals. Injection of pFF resulted in a decline of plasma FSH concentrations in intact and castrated males and in intact females, but did not influence plasma LH concentrations. These data demonstrate a sex-specific difference in the control of plasma FSH, but not in plasma LH concentration in the neonatal pig. Plasma FSH concentrations, but not plasma LH concentrations, are suppressed by testicular hormones in 1-wk-old piglets. Plasma FSH concentrations can be suppressed in both neonatal male and female pigs by injections of pFF.     

Plasma concentrations of testosterone and LH in the male dog

Blood samples were withdrawn every 20 min from 3 conscious intact and 2 castrated mature males during non-consecutive periods of 12 h during the light and dark phases of the lighting schedule (intact dogs) and of 11 h during the light period (castrated dogs). In the intact dogs testosterone concentrations ranged from 0.4 to 6.0 ng/ml over the 24-h period. LH concentrations varied from 0.2 to 12.0 ng/ml. In all animals, LH peaks were clearly followed, after about 50 min, by corresponding testosterone peaks, but no diurnal rhythm could be established. LH concentrations in the castrated dogs were high (9.8 +/- 2.7 (s.e.m.) ng/ml), and still showed an episodic pattern in spite of the undetectable plasma testosterone levels.     

Disparate effects of endogenous and exogenous oestradiol on luteal phase function in women

Five normally ovulating women were induced to superovulate with pulsatile 'pure' FSH (28 i.u. every 3 h by a s.c. pump), and another 5 women were given an i.m. injection of 10 mg oestradiol benzoate in the late follicular phase. Serum oestradiol concentrations in the luteal phase were similar in both groups and significantly higher than in corresponding control cycles. The luteal phase was of shorter duration in the FSH (11.2 +/- 0.7 days) than in the control (13.4 +/- 0.2 days) and the oestrogen-treatment cycles (13.4 +/- 0.7 days) (P less than 0.05, mean +/- s.e.m.). FSH cycles had significantly lower early luteal serum LH (Day 1: 5.3 +/- 1.5 mi.u./ml) and mid-luteal serum progesterone values (35.4 +/- 3.5 nmol/l) compared with the control (27.8 +/- 5.8 mi.u./ml and 65.4 +/- 5.7 nmol/l, respectively) and oestrogen treatment cycles (25.3 +/- 8.3 mi.u./ml and 59.1 +/- 8.4 nmol/l, respectively) (P less than 0.05, mean +/- s.e.m.). These results suggest that, in hyperstimulated cycles, the luteal phase can be disrupted even without follicle aspiration, and that suppression of endogenous LH secretion may be responsible.     

Changes in serum testosterone and estradiol concentrations following acute androstenedione ingestion in young women.

The effect of androstenedione intake on serum hormone concentrations in women is equivocal. Therefore, we examined the hormonal response to androstenedione intake in healthy young (22.1 +/- 0.4 y) women for 4 hours. On day 3 of the follicular phase, subjects ingested placebo, 100, or 300 mg androstenedione in a random, double-blind, cross-over manner. Blood samples were collected before and every 30 min for 240 min after intake. Serum androstenedione concentrations (means +/- SE) increased above basal (6.2 +/- 0.8 nmol/l) from 60-240 min for both 100 mg (22.6 +/- 1.0 nmol/l at 240 min) and 300 mg (28.1 +/- 1.3 nmol/l at 210 min). Androstenedione intake increased serum total testosterone concentrations above basal (1.2 +/- 0.2 nmol/l) from 120-240 min (5.5 +/- 0.9 nmol/l at 210 min) with 100 mg and from 60-240 with 300 mg (10.2 +/- 1.6 nmol/l at 210 min). Androstenedione intake also increased serum estradiol concentrations (basal 191 +/- 24 pmol/l) at 150 min with 100 mg (237 +/- 35 pmol/l) and from 150-240 min with 300 mg (reaching 260 +/- 32 pmol/l at 240 min). These data indicate that, in contrast to men, androstenedione intake in women increases serum testosterone concentrations.     

Follicular activity and hormonal secretory profile in vicuna (Vicugna vicugna)

The objective of the present study was to characterize ovarian activity in non-mated vicunas, relating ovarian structures (evaluated by transrectal ultrasonography, daily for 30 days) to changes in plasma concentrations of estradiol-17beta and progesterone. Ovarian follicular activity occurred in waves, characterized by the follicle emergence, growth and regression. The mean duration of follicular waves was 7.2+/-0.5 days (mean+/-S.E.M.), with a range of 4-11 days. The follicular growth phase averaged 3.0+/-0.2 days, the static phase 1.4+/-0.1, the regression phase 2.9+/-0.3 days, and the inter-wave interval was 4.2+/-0.3 days. The mean growth rate during the growing phase was 1.8+/-0.1mm/day, while the duration of the interval from 6mm to maximum diameter was 1.4+/-0.1 days. The mean maximum diameter of the dominant follicle was 8.4+/-0.3mm (range: 6.2-11.2) and mean diameter of the largest subordinate follicle was 5.4+/-0.1mm. There was an inverse relationship between the size of the largest follicle and the total number of follicles (r=-0.21, P=0.002). Follicle activity alternated between ovaries in 77% of the waves, with 40% of dominant follicles present in the left ovary and 60% in the right ovary. Plasma estradiol-17beta concentrations also had a wave-like pattern, varying between 12.0 and 62.8 pmol/l. Plasma progesterone concentrations remained below 5.0 nmol/l and there was no ultrasonographic evidence of ovulation during the study.     

Social Context Influences Androgenic Effects on Calling in the Green Treefrog (Hyla cinerea)

Courtship behavior in frogs is an ideal model for investigating the relationships among social experience, gonadal steroids, and behavior. Reception of mating calls causes an increase in androgen levels in listening males, and calling, in turn, depends on the presence of androgens. However, previous studies found that androgen replacement does not always restore calling to intact levels, and the relationship between androgens and calling may be context dependent. We examined the influence of androgens on calling behavior in the presence and the absence of social signals in male green treefrogs (Hyla cinerea). We categorized calling during an acoustic stimulus (mating chorus or tones) as evoked and calling in the absence of a stimulus as spontaneous. Intact males received a cholesterol implant, castrated males were castrated and received a cholesterol implant, and T-implanted males were castrated and received a testosterone implant. The androgen levels (mean +/- SE ng/ml of plasma) achieved by the implants were as follows: castrated males, 1.2 +/- 0.2; intact males 21.9 +/- 7.0; T-implanted males, 254.6 +/- 39.5. As in other frogs, calling depends on the presence of androgens, as castration abolished and T replacement maintained calling. However, among intact and T-implanted males, the influence of androgens on calling differed between spontaneous and evoked calling. There was a positive effect of androgen treatment on spontaneous call rate and a positive correlation between spontaneous call rate and androgen levels. The influence of androgen levels on evoked call rate was more complex and interacted with acoustic treatment. Surprisingly, T implants suppressed the chorus-specific increase in calling that is evident in intact males. In addition, in response to the chorus, T-implanted males called less than did intact males, in spite of higher androgen levels. Furthermore, variation in androgens did not explain variation in evoked call rate. These data indicate that androgens influence the motivation to call, but that, when socially stimulated, androgens are necessary but insufficient for calling.     

Exposure to ovarian steroids elicits a female pattern of plasma cortisol levels in castrated male macaques.

Our recent observations (1) that there is a difference in circadian patterns of plasma cortisol levels between male and female macaques and (2) that after gonadectomy these differences in the patterns and in the levels of cortisol were reduced prompted us to investigate how 17 beta-estradiol (E2) and progesterone affect cortisol secretion in orchidectomized male rhesus macaques. Five male macaques, castrated as adults, were implanted subcutaneously with segments of silastic tubing filled with E2 and with progesterone in a manner such that the levels and the sequence of these hormones mimicked those that occur during the menstrual cycle of intact female macaques. Since previous studies had shown that the difference in cortisol patterns was due to higher levels in females during the day, these studies were conducted from 0800 to 2000 hours. Blood samples were collected in an adjacent room at 15-minute intervals. Separate trials were conducted 2 weeks after E2 was implanted and levels were 110 +/- 14 pg/ml and again 2 weeks later after progesterone was implanted and E2 levels were 59 +/- 15 pg/ml; progesterone levels averaged 4.0 +/- 0.65 ng/ml. Mean plasma concentrations of cortisol (microgram/100 ml) for the 12-hour period were three-fold higher in orchidectomized males treated with E2 (17.2) and with E2 + progesterone (18.0) than in intact males (4.9). Levels in males treated with ovarian steroids were double that (8.5 micrograms/100 ml) observed for intact females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in the levels of growth hormones, insulin, cortisol, thyroxine and somatomedin-C/IGF-1, with increasing gestational age in the fetal pig, and the effect of thyroidectomy in utero

1. Blood samples were taken from 30 chronically catheterized pig fetuses in utero. Levels of growth hormone, insulin, cortisol, thyroxine and somatomedin-C/IGF-1 were measured in the plasma of intact fetuses and the plasma of thyroidectomized fetuses at various gestational ages during the latter part of pregnancy. 2. Growth hormone levels were high (mean +/- SEM: 83 +/- 9 ng/ml and remained constant throughout this period. 3. Insulin levels were also constant and ranged between 4 and 14 mU/l. 4. Cortisol levels showed a general increase from 400 nmol/l at 97 days to 1200 nmol/l at term and this increase was not affected by thyroidectomy. 5. IGF-1 levels were lower than in the sows (48.0 +/- 3.0 ng/ml) and did not change throughout this period. 6. Thyroxine levels were also unchanged at about 92 +/- 4 nmol/l. 7. Thyroidectomy resulted in lower (P less than 0.001) thyroxine levels (28 +/- 3 nmol/l) but had no effect on the levels of any other hormone.     

Androgenic control of immunoreactive somatostatin in the Harderian gland of the Syrian hamster

Harderian glands of Syrian hamsters contained measurable levels of immunoreactive somatostatin. After an extraction procedure, serial dilutions of tissue were assayed and showed parallelism in the displacement curve with dilutions of purified somatostatin standard in the radioimmunoassay. Somatostatin concentrations were higher in female hamsters (10.0 +/- 2.1 ng/mg protein) than in males (2.6 +/- 0.4 ng/mg protein). Castrated males had somatostatin values in the range of females (12.4 +/- 2.3 ng/mg protein) at 1 month after gonadectomy. Testosterone implants prevented the rise of Harderian gland somatostatin in castrated males. Gonadectomized males had lower somatostatin content in the gland than did control males (1.0 +/- 0.2 ng/mg protein) at 2 months after castration. Somatostatin values in females were unaffected by gonadectomy, but there were variations during the oestrous cycle, with a nadir detected at dioestrus-1 and maximal values coincident with the day of the ovulation.     

Hormone concentrations before and after semen-induced ovulation in the bactrian camel (Camelus bactrianus)

During the follicular phase of bactrian camels, basal concentrations of LH were 2.7 +/- 1.2 ng/ml. By 4 h after insemination peak values of 6.9 +/- 1.0 ng/ml occurred. In addition, a smaller LH peak (5.4 +/- 2.5 ng/ml) appeared 1 day before regression of the follicle began in unmated camels. During the follicular phase peripheral plasma progesterone values were low (0.36 +/- 0.28 ng/ml), but values increased to reach 1.73 +/- 0.74 ng/ml at 3 days and 2.4 +/- 0.86 ng/ml at 7 days after ovulation. Plasma oestradiol-17 beta concentrations were 26.8 +/- 9.0 pg/ml during the follicular phase and 30.8 +/- 5.1 pg/ml when the follicle was maximum size. Values fell after ovulation but rose to 29.8 +/- 6.5 pg/ml 3 days later.     

Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.     

Treatment with tetrahydrobiopterin reduces blood pressure in male SHR by reducing testosterone synthesis

Treatment with tetrahydrobiopterin (BH(4)) reduces blood pressure in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that chronic BH(4) reduces blood pressure in male SHR by reducing testosterone biosynthesis mediated by increasing nitric oxide (NO). Male SHR, aged 17-18 wk, intact or castrated, were treated for 1 wk with BH(4) (20 mg.kg(-1).day(-1) ip). After 1 wk, mean arterial pressure (MAP), serum testosterone, and nitrate/nitrite excretion (NO(x)) were measured. MAP was significantly higher in intact males than castrated males (179 +/- 2 vs. 155 +/- 4 mmHg, P < 0.001). In intact males, BH(4) caused a 17% reduction in MAP (148 +/- 2 mmHg), had no effect on NO(x), and reduced serum testosterone by 85% (24.09 +/- 2.37 vs. 3.72 +/- 0.73 ng/dl; P < 0.001). In castrated males, BH(4) had no effect on MAP (152 +/- 5 mmHg) but increased NO(x) by 38%. When castrated males were supplemented with testosterone, MAP increased to the same level as in intact males (180 +/- 7 mmHg), and BH(4) had no effect on MAP (182 +/- 7 mmHg) or NO(x). NO has been shown to decrease testosterone biosynthesis. Chronic sodium nitrite (70 mg.kg(-1).day(-1) x 1 wk) decreased MAP in intact males (150 +/- 4 mmHg) but had no effect on serum testosterone (21.46 +/- 3.08 ng/dl). The data suggest that BH(4) reduces testosterone synthesis and thereby reduces MAP in male SHR, an androgen-dependent model of hypertension. The mechanism(s) by which BH(4) reduces serum testosterone levels are not clear, but the data do not support a role for NO as a mediator.     

Serum thyroxine and triiodothyronine radioimmunoassay values in the normal ferret

The European ferret, Mustela putorius furo, has become increasingly popular as an animal model in biomedical research. However, certain important normal clinical data have not been established for the ferret. In this study, serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) values were obtained from ferrets by the use of commercial radioimmunoassays. Sera from 44 animals, 31 males (27 intact and 4 castrated) and 13 females (10 intact and 3 spayed) were assayed. Serum T4 values ranged from 1.01-8.29 micrograms/dl for males (mean = 3.24 +/- 1.65 micrograms/dl), and 0.71-3.43 micrograms/dl for females (mean = 1.87 +/- 0.79 micrograms/dl). Serum T4 values of adult female ferrets, juvenile ferrets (less than 1 year old) of either sex, and castrated males were similar to the normal T4 values of the cat, 1.20-3.80 micrograms/dl. Intact adult male ferrets had higher serum T4 values which were more comparable to those of the normal dog 1.52-3.60 micrograms/dl. Serum T3 values ranged from 0.45-0.78 ng/ml for males (mean = 0.58 +/- 0.09 ng/ml), and 0.29-0.73 ng/ml for females (mean = 0.53 +/- 0.13 ng/ml). These values are comparable to those of dogs and cats which are 0.50-1.50 ng/ml.     

Gender difference in C-reactive protein concentrations in individuals with atherothrombotic risk factors and apparently healthy ones.

Recent studies have shown that C-reactive proteins have a pathogenetic role in atherothrombosis and concentrations of these substances could be used as a marker for future vascular events. The objective of this study was to determine gender differences in highly sensitive C-reactive protein (hs-CRP) in individuals with atherothrombotic risk factors and apparently healthy ones. We have presently matched 469 females and 469 males having the same age and body mass index (BMI). Of these, 210 men and 210 women had no atherothrombotic risk factors. In this group the hs-CRP concentrations were 1.6+/-3.4 mg l(-1) in women and 1.0+/-2.7 mg l(-1) in men (p<0.0005). These values were 2.1+/-3.4 mg l(-1) and 1.5+/-2.8 mg l(-1), respectively, in the entire cohort (p<0.0005), which included also individuals with atherothrombotic risk factors. We conclude that significant gender differences exist in hs-CRP concentrations despite perfect matching for age and BMI. These differences should be reflected in guidelines that suggest hs-CRP cut-off points for the stratification of vascular risk.     

Cyclic changes of plasma spermine concentrations in women

Based on previous studies which suggest that blood polyamines fluctuate during the menstrual cycle, the present study was set to determine whether plasma concentrations of the polyamine spermine show menstrual cycle-associated changes and if so, how these changes relate to phasic variations in other female hormones. Blood samples were collected from a group of 9 healthy women of various ages at 5 defined periods during their menstrual cycle including 1 woman on oral contraceptives. Spermine concentrations were determined in plasma acid extracts by reversed-phase high performance liquid chromatography method. Plasma estradiol, LH and FSH were measured by microparticle enzyme immunoassay using an automatic analyzer. Spermine concentrations, 104.4 +/- 12.2 nmol/ml at 1-3 day of the cycle, were increased transiently with a peak (263.8 +/- 22.1 nmol/ml) at 8-10 day and declined to 85.4 +/- 29.8 nmol/ml by 21-23 day of the cycle. The peak spermine concentrations coincided with the first increase in plasma estrogen levels. The individual variations in the temporal profile of spermine concentrations were of similar magnitude as individual differences in other female hormones. We conclude that: a) Plasma spermine concentrations undergo distinct cyclic alterations during the menstrual cycle with peak concentrations coinciding with the first estradiol increase, and b) Peak plasma spermine concentrations occur during the follicular phase, just prior to ovulation, during the period of rapid endometrial growth.     

Perturbation of estradiol-feedback control of luteinizing hormone secretion by immunoneutralization induces development of follicular cysts in cattle

We used immunoneutralization of endogenous estradiol to investigate deficiencies in the estradiol-feedback regulation of LH secretion as a primary cause of follicular cysts in cattle. Twenty-one cows in the prostaglandin (PG) F(2alpha)-induced follicular phase were assigned to receive either 100 ml of estradiol antiserum produced in a castrated male goat (n = 11, immunized group) or the same amount of castrated male goat serum (n = 10, control group). The time of injection of the sera was designated as 0 h and Day 0. Five cows in each group were assigned to subgroups in which we determined the effects of estradiol immunization on LH secretion and follicular growth during the periovulatory period. The remaining six estradiol-immunized cows were subjected to long-term analyses of follicular growth and hormonal profiles, including evaluation of pulsatile secretion of LH. The remaining five control cows were used to determine pulsatile secretion of LH on Day 0 (follicular phase) and Day 14 (midluteal phase). The control cows exhibited a preovulatory LH surge within 48 h after injection of the control serum, followed by ovulation of the dominant follicle that had developed during the PGF(2alpha)-induced follicular phase. In contrast, the LH surge was not detected after treatment with estradiol antiserum. None of the 11 estradiol-immunized cows had ovulation of the dominant follicle, which had emerged before estradiol immunization and enlarged to more than 20 mm in diameter by Day 10. Long-term observation of the six immunized cows revealed that five had multiple follicular waves, with maximum follicular sizes of 20-45 mm at 10- to 30-day intervals for more than 50 days. The sixth cow experienced twin ovulations of the initial persistent follicles on Day 18. The LH pulse frequency in the five immunized cows that showed the long-term turnover of cystic follicles ranged from 0.81 +/- 0.13 to 0.97 +/- 0.09 pulses/h during the experiment, significantly (P < 0.05) higher than that in the midluteal phase of the control cows (0.23 +/- 0.07). The mean LH concentration in the immunized cows was also generally higher than that in the luteal phase of the control cows. However, the LH pulse and mean concentration of LH after immunization were similar to those in the follicular phase of the control cows. Plasma concentrations of total inhibin increased (P < 0.01) concomitant with the emergence of cystic follicles and remained high during the growth of cystic follicles, whereas FSH concentrations were inversely correlated with total inhibin concentrations. In conclusion, neutralization of endogenous estradiol resulted in suppression of the preovulatory LH surge but a normal range of basal LH secretion, and this circumstance led to an anovulatory situation similar to that observed with naturally occurring follicular cysts. These findings provide evidence that lack of LH surge because of dysfunction in the positive-feedback regulation of LH secretion by estradiol can be the initial factor inducing formation of follicular cysts.     

Threshold for behavioral response to testosterone in old castrated male rhesus macaques

The sexual behaviors of old, intact (N = 5) and old, castrated (N = 6) rhesus macaque males were compared in six series of pair tests with receptive females. The castrated monkeys were tested when untreated and when given five doses of testosterone propionate (TP; 0.004, 0.016, 0.064, 0.256, and 1.024 mg/kg of body weight) in consecutive months. The serum testosterone (T) level was determined for each male before and after each series of tests. When untreated, none of the castrated males ejaculated, and yawning was significantly less in these monkeys than in intact males-no other behavioral measures differed significantly. Within 2 weeks of daily injections of 0.004 mg of TP/kg, two males ejaculated, and all differences in measures of ejaculation were eliminated. A third male ejaculated after 1 week of treatment with 0.016 mg of TP/kg. Yawning values did not differ during and after treatment with 0.064 mg of TP/kg. Although final mean serum T levels were six times higher in castrated (24.3 ng/ml) than in intact males (4.2 ng/ml), sexual performance levels did not exceed those of intact males.     

Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A

Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabète-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.