A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women.

Irisin, a newly discovered, PGC-1α dependent myokine, has recently been shown to increase in circulation in response to sprint exercise. This study examined the effect of prolonged exercise on irisin concentrations in young men (n=7) as well as in young women (n=5) during different stages of the menstrual cycle. Seven young men completed 90 min of treadmill exercise at 60% of VO2max and a resting control trial. Five women completed the same exercise protocol in two different trials: during the early follicular phase and mid-luteal phase of the menstrual cycle. Blood samples were collected and analyzed for irisin concentrations immediately before exercise, at 54 and 90 min of exercise, and at 20 min of recovery (R20). Findings revealed that by 54 min of a 90 min treadmill exercise protocol at 60% of VO2max, irisin concentrations significantly increased 20.4% in young men and 20.3% as well as 24.6% in young women during the early follicular and mid-luteal phases of the menstrual cycle, respectively. However, by 90 min of exercise as well as R20, irisin concentrations were no longer elevated. Stage of the menstrual cycle did not affect responses in young women. Findings indicate that prolonged aerobic exercise produces a transient increase in irisin concentrations during the first hour of exercise for both genders and suggest that this form of moderate exercise may be helpful in improving fat metabolism.

Effect of hydration state on testosterone and cortisol responses to training-intensity exercise in collegiate runners.

Exercise intensity powerfully influences testosterone, cortisol, and testosterone : cortisol ratio (T:C) responses to endurance exercise. Hydration state may also modulate these hormones, and therefore may alter the anabolic/catabolic balance in response to endurance exercise and training. This study examined the effect of running intensity on testosterone, cortisol, and T : C when exercise was initiated in a hypohydrated state. Nine male collegiate runners (age = 20 +/- 0 y, height = 178 +/- 2 cm, mass = 67.0 +/- 1.8 kg, body fat % = 9.8 +/- 0.7 %, V.O2max = 65.7 +/- 1.1 ml.kg (-1).min (-1)) completed four 10-min treadmill runs differing in pre-exercise hydration status (euhydrated, or hypohydrated by 5 % of body mass) and exercise intensity (70 % or 85 % V.O2max). Body mass, urine osmolality, and urine-specific gravity documented fluid balance; blood samples drawn pre-, immediately post-, and 20 min post-exercise were analyzed for testosterone, cortisol, and T : C. Except for heart rate measured during the 70 % V.O2max trials, heart rate, V.O2, and plasma lactate were similar between euhydrated and hypohydrated conditions for a given intensity, suggesting hypohydration did not measurably increase the physiological stress of the exercise bouts. Furthermore, hydration state had no measurable effect on testosterone concentrations before, during, or after exercise at either intensity. Regardless of exercise intensity, cortisol concentrations were greater during hypohydration than euhydration pre-exercise and 20 min post-exercise. Additionally, T : C was significantly lower 20 min post-exercise at 70 % V.O2max when subjects were initially hypohydrated (T : C = 0.055) versus euhydrated (T : C = 0.072). These findings suggest that depending on exercise intensity, T : C may be altered by hydration state, therefore influencing the balance between anabolism and catabolism in response to running exercise performed at typical training intensities.

A study to determine if acute maternal and fetal hyperglycemia/insulinemia induces leptin production during pregnancy.

BACKGROUND: In pregnant primates, the effect of post-prandial hyperglycemic or insulinemic states on leptin production is not known. Our goal was to conduct a controlled study using an established pregnant baboon model ( PAPIO ANUBIS) to determine whether acute glucose changes would have an effect on maternal or fetal plasma leptin levels. METHODS: Two animals were operated on at 138 and 140 days of gestation (term approximately 184 days) by placing 4 cannulae in the maternal aorta, inferior vena cava, fetal carotid artery, and the amniotic cavity. At 145 and 150 days, glucose infusions were started via the maternal femoral vein. Animal 1 received 7.5 gm of glucose over a 2-hour period at 145 th day. Animal 2 received 20 gm of glucose over a 1-hour period at 150th day. Both animals remained ad libitum throughout the experiments. Maternal and fetal blood samples were obtained from the arterial lines before the glucose infusion and at half hour intervals to include 30 minutes post-infusion. RESULTS: Significant changes from baseline concentrations were observed for maternal and fetal glucose and insulin concentrations in response to both glucose challenges. Maternal and fetal plasma leptin concentrations did not correlate with glucose or insulin changes. CONCLUSION: This preliminary study demonstrated that in primates, acute changes in circulating maternal or fetal glucose or insulin concentration do not affect maternal or fetal plasma leptin concentrations. These results suggest that alterations in leptin secretion by the maternal-placental-fetal unit may only occur in pathological states.

Changes in serum inhibin B during normal male puberty.

OBJECTIVE: In adult men, inhibin B (InhB) regulates FSH secretion by a negative feedback. The aims of this study were to evaluate the changes of InhB during puberty in the male and the relationship between InhB and FSH, LH, testosterone and testicular volume. DESIGN: Cross-sectional study. METHODS: InhB was measured using a two-site ELISA in 100 healthy boys subdivided by their pubertal development according to Tanner into five groups of 20. RESULTS: During puberty we observed an increase of InhB level (G1 = 84.3 pg/ml, G3 = 132.2 pg/ml, G5 = 206.1 pg/ml). In G1, InhB correlated positively with FSH (P = 0.0001), LH (P = 0.005), testosterone (P = 0.001) and testicular volume (P = 0.007); in G5, InhB correlated inversely with FSH (P = 0.001) and LH (P = 0.045) and directly with testicular volume (P = 0.013). The multivariate analysis demonstrated that: in G1, FSH is the most important, and testosterone the second most significant, stimulus for InhB increase; in G2 only FSH has a positive effect on InhB variation; in G3 only mean testicular volume fits the model (G1-G3: InhB dependent variable); considering the FSH dependent variable, in G4, InhB is the most important stimulus for FSH decrease and mean testicular volume is a secondary directly proportional variable; in G5, only InhB shows a significant inverse relationship with FSH. CONCLUSIONS: During puberty there is a regular increase of InhB. In the first phases of gonadal maturation, InhB and FSH correlate positively, while in mid-late stages the relationship is inverse. We found that in mid-puberty (G3-G4), the serum concentration of InhB increases, as its inverse relationship with FSH is being established and hence spermatogenesis.

Low pregnancy-associated plasma protein-a at 10(+1) to 14(+6) weeks of gestation and a possible mechanism leading to miscarriage.

OBJECTIVE: To compare pregnancy-associated plasma protein-A (PAPP-A) serum levels at 10(+1) to 14(+6) weeks gestation in groups of patients with different obstetrical outcomes. PATIENTS AND METHODS: The medical records of women who had consented to donate blood for biochemical research purposes while their pregnancies were uncomplicated were reviewed to define the clinical groups. After the clinical groups were defined, the donated maternal serum samples were thawed and PAPP-A measured by ELISA. ANOVA was used to compare mean values within groups. RESULT: All groups had similar gestational ages at blood donation (overall mean 12.5 weeks; no difference in gestational age was found within groups, p = 0.18). The overall PAPP-A serum level was 2.01 mIU/ml with only the spontaneous abortion group having a statistical different PAPP-A level (0.09 mIU/ml; p < 0.001). CONCLUSION: These data suggest that those women who experienced spontaneous abortions had significantly different mean PAPP-A serum levels at 10(+1) to 14(+6) weeks gestation. Several lines of evidence suggest that downregulation of insulin-like growth factor-II availability due to a decreased PAPP-A serum level may be the cause of spontaneous abortion in these women.

Ghrelin and other glucoregulatory hormone responses to eccentric and concentric muscle contractions.

OBJECTIVE: Heavy resistance exercise increases growth hormone (GH) and blood glucose levels. Ghrelin is an endogenous ligand for the GH secretagory receptor that stimulates growth hormone release. Circulating ghrelin levels are suppressed by insulin and glucose. The study was conducted to determine effects of concentric (CON) and eccentric (ECC) muscle actions at the same absolute workload on circulating ghrelin and glucose as well as related glucoregulatory peptides. METHODS: Ten-RM loads for bench press, leg extension, military press, and leg curl were obtained from nine males, mean age 25. +/- 1.2 yr and body fat 17.2 +/- 1.6%. Subjects then completed two experimental trials of either CON or ECC contractions at the same absolute workload. Subjects performed four sets of 12 repetitions for each exercise at 80% of a 10-RM with 90 s rest periods. A pulley system or steel levers were positioned on each machine to raise or lower the weight so only CON or ECC contractions were performed. Pre-, post-, and 15-min post-exercise blood samples were collected. RESULTS: Ghrelin did not increase in response to either muscle action and actually declined during the CON trial. Glucose and insulin increased regardless of the form of muscle action, but amylin and C-peptide did not change. CONCLUSIONS: Data indicate that ghrelin does not contribute to moderate resistance exercise-induced increases in growth hormone, whether from CON or ECC muscle actions. Results suggest that with a moderate loading protocol both CON and ECC muscle actions performed at the same absolute workload elevate glucose and insulin concentrations, but are not related to post-CON exercise ghrelin suppression.

Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy.

Leptin produced by both adipose tissue and the placental trophoblast, has been proposed to regulate numerous aspects of human conceptus development. Although recent animal studies have suggested an additional role for the polypeptide in fetal lung maturation, no evidence has been reported in primates. Therefore, we employed the baboon (Papio sp.), a well-characterized primate model for human pregnancy, to determine the presence and ontogeny of leptin receptor in fetal lung with advancing gestation. Lungs were collected from fetal baboons, early in gestation (days 58-62, n = 4), at mid gestation (days 98-102, n = 4), and late in gestation (days 158-165, n = 4) (term 184 days). mRNA transcripts for leptin (LEP) and both long and short intracellular domain isoforms of the leptin receptor (LEP-R(L) and LEP-R(S)) were assessed by RT-PCR. leptin receptor protein was evaluated by immunoblotting and cell types expressing leptin receptor were identified in late pregnancy by immunohistochemistry. Fetal serum leptin concentrations, determined by RIA, remained relatively unchanged at 5.7 +/- 1.1 ng/ml (mean +/- s.e.m.) in mid pregnancy and 8.4 +/- 3.0 ng/ml in late pregnancy (P > 0.05). Although leptin were detectable in fetal lung, no changes in transcript abundance were apparent with advancing gestation. However, transcripts for both LEP-R(L) and LEP-R(S) receptor isoforms increased several-fold (P < 0.05) in fetal lung between mid and late gestation, while leptin receptor protein was detectable only in late pregnancy. leptin receptor was localized in distal pulmonary epithelial cells, including type II pneumocytes. In conclusion, leptin is present in the fetal baboon and its receptor is enhanced during late gestation in cells responsible for the synthesis of pulmonary surfactant. Collectively, these and past findings may suggest a modulatory role for the polypeptide in pulmonary development and/or may identify leptin receptor as a physiological marker of primate fetal lung maturity.

Rigorous running increases growth hormone and insulin-like growth factor-I without altering ghrelin.

It has been suggested that ghrelin may play a role in growth hormone (GH) responses to exercise. The present study was designed to determine whether ghrelin, GH, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were altered by a progressively intense running protocol. Six well-trained male volunteers completed a progressively intense intermittent exercise trial on a treadmill that included four exercise intensities: 60%, 75%, 90%, and 100% of Vo2max. Blood samples were collected before exercise, after each exercise intensity, and at 15 and 30 mins following the exercise protocol. Subjects also completed a separate control trial at the same time of day that excluded exercise. GH changed significantly over time, and GH area under the curve (AUC) was significantly higher in the exercise trial than the control trial. Area under the curve IGF-I levels for the exercise trial were significantly higher than the control trial. There was no difference in the ghrelin and IGFBP-3 responses to the exercise and control trials. Pearson correlation coefficients revealed significant relationships between ghrelin and both IGF-I and IGFBP-3; however, no relationship between ghrelin and GH was found. In conclusion, intense running produces increases in total IGF-I concentrations, which differs from findings in previous studies using less rigorous running protocols and less frequent blood sampling regimens. Moreover, running exercise that produces substantial increases in GH does not affect peripheral ghrelin levels; however, significant relationships between ghrelin and both IGF-I and IGFBP-3 exist during intense intermittent running and recovery, which warrants further investigation.

Responses of growth hormone aggregates to different intermittent exercise intensities.

The purpose of this study was to determine the impact of high-intensity intermittent exercise on the presence of circulating growth hormone (GH) aggregates measured using two different assay techniques. Six male subjects with endurance training background participated in this study under both exercise and no-exercise control conditions. After resting blood sampling, subjects completed an intermittent treadmill exercise protocol at four speeds predicted to elicit a specific VO(2):60% VO(2max) for 10 min, 75% for 10 min, 90% for 5 min, and 100% for 2 min. After each exercise intensity was completed treadmill speed was reduced to a walk (3.5-4 min) for blood sampling. Sampling continued every 15 min for 1 h into recovery. All samples were then measured for GH concentrations using Nichols immunoradiometric assay (IRMA) and Diagnostic Systems Laboratory's immunofunctional assay (IFA). A second set of samples was chemically reduced using reduced glutathione (GSH; 10 mM for 18 h at room temperature) to break disulfide bonds between possible oligomeric GH complexes, and subsequently assayed using the same GH assays. With the IRMA, GH was significantly elevated ( P<0.05) after the 75% workload and remained elevated through 30 min post-exercise. After adding GSH to the sample, the IRMA indicated significant increases in GH as early as the 60% exercise intensity and remained elevated through 45 min into recovery. At 75%, the GSH assay run was significantly higher than the non-GSH assay run. With the IFA, GH was significantly elevated at 60% in the non-GSH condition, whereas the GSH assay run indicated significant elevations at 75%. Both GSH and non-GSH conditions remained elevated through 30 min into recovery. These data indicate that the addition of GSH to serum samples prior to assay via an IRMA may break existing disulfide bonds between aggregated GH molecules, thus altering the apparent assay signal to reveal greater total GH in the sample.

Leptin and thyroxine during sexual development in male monkeys: effect of neonatal gonadotropin-releasing hormone antagonist treatment and delayed puberty on the developmental pattern of leptin and thyroxine secretion.

OBJECTIVE: Neonatal treatment of male monkeys with a gonadotropin-releasing hormone antagonist (Ant) increased the incidence of delayed puberty. Using blood samples that had been collected from monkeys with normal or delayed puberty, we assessed the potential involvement of leptin and thyroxine (T4) in sexual development. DESIGN AND METHODS: Monkeys were treated from birth until 4 months of age with vehicle, Ant or Ant/androgen and blood samples were drawn from 10 to 62 months of age. RESULTS: Serum leptin and total T4 concentrations declined in parallel throughout adolescence in all treatment groups. There was no transient rise in leptin before or in association with the onset of puberty. Also, leptin did not differ during the peripubertal period between animals experiencing puberty at that time versus those in which puberty was being delayed. Neonates treated with Ant either alone or with androgen replacement had higher leptin levels than controls throughout development. While leptin exhibited no significant changes during the peripubertal period, T4 values increased and declined in parallel with the peripubertal changes in hypothalamic-pituitary-testicular activity. CONCLUSIONS: These data do not support the concept that a transient rise in leptin triggers the onset of puberty in male monkeys. However, the disruption of neonatal activity of the pituitary-testicular axis alters the developmental pattern of leptin. The changes in T4 levels during the peripubertal period suggest that thyroid status may be a significant contributor to the process of sexual development in the male monkey and that peripubertal changes in secretion of this hormone may serve as an effective physiological response during a critical period of elevated energy expenditure.

Glucoregulatory endocrine responses to intermittent exercise of different intensities: plasma changes in a pancreatic beta-cell peptide, amylin.

Amylin, a peptide hormone released from the beta cells of the pancreas and cosecreted with insulin, is reported to inhibit the release of postprandial glucagon and insulin and to modulate gastric emptying. Changes in insulin and glucagon are important for controlling blood glucose levels under conditions in which metabolic rate is elevated, such as during and following exercise. Amylin may participate in the regulation of blood glucose levels in response to exercise, although the role of amylin has not been investigated. The purpose of the study was to determine the effects of a progressive, intermittent exercise protocol on amylin concentrations and to compare its response to circulating levels of insulin, glucagon, cortisol, and glucose. Seven well-trained males completed an intermittent exercise trial on a treadmill at four progressive exercise intensities: 60%, 75%, 90%, and 100% of maximum oxygen consumption (.VO(2)max). Blood samples were collected before exercise, after each exercise intensity, and for 1 hour following the exercise protocol. Subjects also completed a control trial with no exercise. Amylin and insulin rose from baseline (5.79 +/-.78 pmol/L and 4.76 +/-.88 microIU/mL) to peak after 100% .VO(2)max (9.16 +/- 1.35 pmol/L and 14.37 +/- microIU/ml), respectively and remained elevated during much of recovery. Thus, a progressive intermittent exercise protocol of moderate to maximum exercise intensities stimulates increases in amylin levels in well-trained individuals in a similar fashion to that of insulin, whereas glucagon concentrations only increase after the greatest exercise intensity, then quickly decline. Future studies should examine the effects of higher amylin concentrations in exercise recovery on glucoregulation.

Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy.

Leptin, a product of both adipose tissue and the placental syncytiotrophoblast and a potential regulator of primate conceptus development, increases in the maternal circulation with advancing gestation. This increase may be potentiated by estrogens, which also increase as pregnancy progresses. In the present study adipose tissue was collected from nonpregnant (n = 5) baboons (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98--102; n = 5), and late (days 158-162; n = 5) pregnancy (term, approximately 184 days). Additionally, placental estrogen production was inhibited in pregnant baboons by the removal of fetal androgen precursors via fetectomy at midgestation, with tissues collected from fetectomized (n = 5) baboons approximately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R(L) and LEP-R(S) isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competitive RT-PCR, and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues. Although LEP transcript abundance in adipose tissues was unchanged as a result of pregnancy or with advancing gestation, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestational age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and androgens (androstenedione and testosterone) were lower (P < 0.0001) in fetectomized baboons than in intact controls. Serum leptin concentrations were unchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissue and increased (P < 0.05) in placenta in fetectomized baboons. Although LEP-R(L) mRNA levels were unchanged after fetectomy, placental LEP-R(S) transcript abundance was lower (P < 0.04) than in pregnancy-intact baboons matched for gestational age. Results suggest that both adipose tissue and the placenta may contribute to maternal hyperleptinemia during normal primate pregnancy. Furthermore, the withdrawal of placental steroids results in the enhanced placental leptin production that is commensurate with a decline in production by sc adipose tissue.

Effect of estrogen on serum DHEA in younger and older women and the relationship of DHEA to adiposity and gender.

This case-controlled study consisted of 2 parts. The objective of part 1 was to determine the relationship between DHEA, body mass index (BMI), and age in young males, young females, and postmenopausal (PM) females. Part 2 examined the effects of estrogen on DHEA by analyzing the relationship between DHEA and age in young females on and off oral contraceptives (OCs) and PM females on and off estrogen or hormone replacement therapy (ERT/HRT). The study was performed at the Obstetrics and Gynecology Clinic, Texas Tech Health Sciences Center-Amarillo, Exercise Physiology Laboratory at Southeastern Louisiana University, and Woman's Health Research Institute, Woman's Hospital, Baton Rouge, LA. Part 1 groups consisted of: (1) young males between the ages of 18 to 40 years; (2) normally cycling females off OCs, ages 18 to 40 years; and (3) PM females older than 40 years not receiving ERT/HRT. Part 2 groups consisted of: (1) normally cycling females on OCs, ages 18 to 40 years;, (2) normally cycling females off OCs, ages 18 to 40 years; (3) PM females 50 years or older not receiving ERT/HRT; and (4) PM females 50 years or older receiving ERT/HRT. The main outcome measure was serum DHEA concentrations. For part 1, there were significant (P <.05) inverse relationships between DHEA and age for young males; young females, off OCs; PM females, no ERT/HRT r = -.44, -.26, and -.25, respectively. There were no significant relationships between DHEA and BMI for any of the groups. DHEA concentrations were significantly higher in young males than young females even after accounting for age. For part 2, DHEA concentrations were significantly higher in young females off OCs compared with young females on OCs, and significantly higher in PM women off ERT/HRT than those on ERT\HRT. There were significant inverse relationships between DHEA and age for young females and PM females on and off ERT/HRT. From these findings, we conclude that there is an inverse relationship between DHEA and age for young males, young females off OCs, and PM females, no ERT/HRT. No relationship between BMI and DHEA was observed in these same 3 groups. These results agree with previous findings in young men, but differ from previous findings in obese young females. The data also suggest that estrogen treatment (OCs and ERT/HRT) suppresses DHEA concentrations in premenopausal and PM females, and that DHEA declines with age in PM females regardless of estrogen treatment.

Leptin and steroid hormone responses to exercise in adolescent female runners over a 7-week season.

The purpose of the study was to investigate the responses of leptin and steroid hormones to maximal exercise in adolescent female runners over a competitive season. Seven adolescent female distance runners completed three testing trials during weeks 1.4 and 7 of their high-school track season. Blood samples were collected before and after a discontinuous graded exercise test to exhaustion (GXT) for each trial. Tests were administered during the subjects' normal training time (3:30 p.m.-5:00 p.m.). Compared to week 1, peak O2 uptake rose significantly during the season and was 10% and 7% higher at weeks 4 and 7, respectively. Levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisol, testosterone, and leptin increased significantly in response to the graded exercise tests. Testosterone levels were also changed over the course of the study. Resting testosterone levels and testosterone responses to exercise in weeks 4 and 7 were both higher than in week 1. Resting concentrations and acute increases of the other hormones were not changed over the season. It appears, therefore, that DHEA, DHEAS, cortisol, testosterone and leptin concentrations increase in response to running in adolescent female runners. Data also suggest that training and/or maturation increases resting testosterone concentrations and testosterone responses to running in adolescent female runners during a training season.

Leptin in pregnancy.

Leptin is a polypeptide hormone that aids in the regulation of body weight and energy homeostasis and is linked to a variety of reproductive processes in both animals and humans. Thus, leptin may help regulate ovarian development and steroidogenesis and serve as either a primary signal initiating puberty or as a permissive regulator of sexual maturation. Perhaps significantly, peripheral leptin concentrations, adjusted for adiposity, are dramatically higher in females than in males throughout life. During primate pregnancy, maternal levels that arise from adipose stores and perhaps the placenta increase with advancing gestational age. Proposed physiological roles for leptin in pregnancy include the regulation of conceptus growth and development, fetal/placental angiogenesis, embryonic hematopoiesis, and hormone biosynthesis within the maternal-fetoplacental unit. The specific localization of both leptin and its receptor in the syncytiotrophoblast implies autocrine and/or paracrine relationships in this endocrinologically active tissue. Interactions of leptin with mechanisms regulating pre-eclampsia and maternal diabetes have also been suggested. Collectively, therefore, reports suggest that a better understanding of the regulation of leptin and its role(s) throughout gestation may eventually impact those causes of human perinatal morbidity and mortality that are exacerbated by intrauterine growth retardation, macrosomia, placental insufficiency, or prematurity.

Effect of particle size on the prolonged action of subcutaneous danazol in male and female rats.

OBJECTIVE: To investigate the effects of two different particle sizes of danazol in male and female rats. DESIGN: Prospective, vehicle-controlled study. SETTING: Undergraduate college research facility and medical research laboratory. ANIMALS: 18 castrated male rats and 18 cycling female rats. INTERVENTION(S): Preparations of danazol with particle sizes of 2.05 microm or 5.2 microm were administered as a single subcutaneous injection of 400 mg/kg to castrated male rats or estrus-cycling females. MAIN OUTCOME MEASURE(S): Serum LH level in males and estrous cycle length in females. RESULT(S): In males, both preparations significantly (P<. 001) suppressed serum LH by day 5 of treatment. Gonadotropin levels remained low throughout the 35-day study in rats that received the larger-particle danazol, whereas LH levels began to increase after 25 days in rats that received smaller-particle danazol. In females, the normal 4- to 5-day estrous cycle interval was prolonged to 38.7 days (P<.001) in those that received the larger-particle danazol and 25.5 days in those that received the smaller-particle danazol. CONCLUSION(S): The results demonstrate the prolonged effectiveness of a single subcutaneous dose of danazol and indicate that one might be able to predict the effective duration of activity by changing the particle size of the danazol administered.

Ethnic differences in androgens, IGF-I and body fat in healthy prepubertal girls.

OBJECTIVE: To examine ethnic differences in adrenal androgen production, IGF-I, and IGFBP-1 and -3 in relation to bone age, insulin, and body composition in healthy prepubertal girls. METHODS: Serum levels of DHEA-S, androstenedione, IGF-I, and IGFBP-1 and -3 were examined in relation to bone age, insulin, and body composition (determined by dual-energy X-ray absorptiometry) in 47 (19 Caucasian, 9 African-American, 19 Mexican-American) healthy prepubertal girls aged 7.5-9.0 years. RESULTS: Age, weight, height, bone age, androstenedione, insulin, glucose:insulin ratios, and IGFBP-3 levels were not statistically different among groups. Mexican-American girls had higher % body fat than African-Americans or Caucasians (P < 0.001). DHEA-S levels in African-Americans were twofold higher than in Caucasians (P = 0.024), although their % body fat was not significantly different (16.1% and 19.4%, respectively; P = 0.138). DHEA-S levels in Mexican-American girls were intermediate. Bone age and weight were significant covariates for DHEA-S levels. Plasma IGF-I levels were also higher in African-American than in Caucasian or Mexican-American girls (P = 0.009). Covariance analysis showed that IGF-I levels were influenced mainly by ethnicity (P = 0.009) and were independent of bone age. Despite similar insulin levels among groups, IGFBP-1 levels were higher in Caucasians than in Mexican-Americans or African-Americans (P < 0.001). CONCLUSIONS: In healthy prepubertal girls, DHEA-S concentrations are higher in African-Americans than in Caucasians or Mexican-Americans, even before any clinical evidence of adrenarche. Furthermore, IGF-I concentrations are higher in African-American girls than in Caucasian or Mexican-American girls which may contribute to the higher DHEA-S levels observed. Conversely, higher DHEA-S and IGF-I levels in African-American girls may be indicative of an influence not only of gonadal but also of adrenal androgens on the GH/IGF-I axis.

Human chorionic gonadotropin administration does not increase plasma androgen levels in patients undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To investigate the effects of hCG administered to patients undergoing controlled ovarian hyperstimulation on levels of ovarian hormones, including androgens. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Six infertile, normally ovulating volunteers. INTERVENTION(S): The women underwent controlled ovarian hyperstimulation with a GnRH agonist and hMG for IVF-ET. After the i.m. administration of hCG (10,000 IU), blood samples were drawn every 6 hours for 4 days. MAIN OUTCOME MEASURE(S): Plasma androstenedione, testosterone, progesterone, and E2 profiles. RESULT(S): Treatment with hMG increased plasma androstenedione and testosterone levels 1.4-fold and 2.6-fold, respectively. The administration of hCG did not increase plasma androstenedione and testosterone levels any further; mean daily levels remained at 2.3 ng/mL and 0.64 ng/mL, respectively. Circadian changes in androstenedione levels were evident after hCG administration. Plasma progesterone levels neared 10 ng/mL 19 hours after hCG administration, plateaued for 24 hours, and increased again thereafter. Plasma E2 levels declined during the first 2 days after hCG administration and then increased, concomitant with the second phase of progesterone elevation. CONCLUSION(S): In patients undergoing controlled ovarian hyperstimulation, androgen levels increased in response to hMG treatment, but no further elevation occurred after hCG administration. The rate of elevation of progesterone levels and the absolute levels achieved were 3-fold and 10-fold higher, respectively, than those observed during spontaneous menstrual cycles.

Endocrinology of preterm labor.

The clinical importance of preterm labor and delivery dictates that we understand the physiology and diagnostic usefulness of endocrine as well as other agents that may be helpful in this regard. Clearly, estrogen and progesterone establish the environment that allows parturition and probably preterm labor to occur. The use of salivary estriol, though not a foolproof test, is becoming more frequent and is commercially available. Fibronectin, though not an endocrine test, has a similar diagnostic usefulness. In the future, we would expect to see CRH and even the use of selective cytokines, probably IL-6, as possible diagnostic tests. Whereas all of these agents have some diagnostic usefulness, none of them can be expected to predict every case of preterm delivery and some battery of tests, not unlike the triple or quadruple tests that are used for prenatal diagnosis of Down syndrome, may be effective and should be examined in the future. The use of these tests, salivary estriol and fetal fibronectin in particular, has already had an effect on management and decision making involved in preterm labor, and the future should give us more options and hopefully, better choices to manage this most difficult condition.

A longitudinal study of leptin during development in the male rhesus monkey: the effect of body composition and season on circulating leptin levels.

The objective of this study was to examine longitudinal changes in serum leptin concentrations during development and to correlate those changes with sexual development in male rhesus monkeys housed under natural environmental conditions. Blood samples were drawn from 8 control animals approximately every other month from 10 to 30 mo of age and thereafter monthly through 80 mo of age. Leptin levels declined through the juvenile period until the onset of puberty and were negatively correlated with body weight. Seven of the eight animals became sexually mature during the breeding season of their fourth year of life. Puberty was delayed in the other animal until the subsequent breeding season. There were no significant fluctuations in leptin levels prior to or in association with the pubertal rise in LH and testosterone (T) secretion. During the peripubertal period, levels of leptin varied between 2 and 3 ng/ml. The animal that exhibited delayed puberty had the lowest body weight and highest leptin levels during this period. With the achievement of sexual maturity, leptin levels varied seasonally, with peak levels in the late winter (Jan-Mar) and a nadir in the late summer (Aug-Sept). A late winter rise in leptin was also evident in most of the animals during Years 2 and 3, but not during Year 4. In the fall of Years 5 and 6, the seasonal rise in leptin concentrations lagged 3-4 mo behind the seasonal increase in LH and T. In the fall of Year 5, but not thereafter, leptin levels were positively related to percent body fat and negatively correlated with lean body mass. The data do not support the hypothesis that increasing leptin concentrations trigger the onset of puberty in the male rhesus monkey. During the juvenile period and after sexual maturation, but not during the peripubertal period, leptin secretion varied with season in the animals; but the environmental factors that cue or drive this rhythm remain to be determined.