Total and free testosterone in plasma of hypo- and agonadal men.

Plasma total testosterone (T), apparently free T and testosterone binding globulin (TeBG) capacity determined in 14 normal men aged 30-40 years were 461 +/- 100 ng/100 ml, 9.4 +/- 3.0 ng/100 ml and 5.7 +/- 1.9 X 10(-8) M, respectively, whereas in 16 hypogonadal men the corresponding values were 38.6 +/- 27.2 ng/100 ml, 0.47 +/- 0.41 ng/100 ml and 10.4 +/- 3.4 X 10(-8) M showing the TeBG capacity significantly higher (p less than 0.001) in hypogonadal than in normal men. Treatment of 5 hypogonadal subjects with 250 mg testosterone enanthate plus 50 mg testosterone propionate decreased (p less than 0.001) the TeBG level from 14.7 +/- 2.5 X 10(-8YM to 8.3 +/- 1.4 X 10(-8) M on day 8 after a single injection. According to this difference in TeBG, the free T fraction in plasma rose from 0.94% to 1.9% of the total T concentration. These results suggest that alteration of total plasma T affected the TeBG capacity. Decreased T levels raised and increased T concentrations suppressed TeBG, but with a delayed response to the changed T concentrations. The initial mean values in 12 patients with prostatic cancer aged 60-74 years were 397 +/- 165 ng/100 ml, 4.05 +/- 1.8 ng/100 ml and 11.9 +/- 3.3 X 10(-8) M, respectively. The TeBG capacity in these patients was significantly higher and the free T concentration significantly lower (p less than 0.001) than those of the younger normal males. After treatment with 12 g diethylstilbestrol diphosphate and orchidectomy, the TeBG increased to 33.3 +/- 13.1 X 10(-8) M and the plasma free T concentration decreased to the minimal value of 0.053 +/- 0.04 ng/100 ml.     

Plasma testosterone concentrations during postnatal development in the male common marmoset

Repeated measurements of plasma testosterone (T) were made in 56 male marmosets from the day of birth until 300 days of age and in 44 adults (greater than 3 years). The resulting profile of plasma T during postnatal development shows higher levels during infancy (1-90 days) followed by a nadir between 100 and 170 days and then a progressive rise in T during puberty. Although T levels of up to 21 ng/ml were measured in infant males, mean levels (+/- SEM) were 5.4 +/- 0.6 ng/ml (days 1-10), declining gradually to 1.7 +/- 0.1 ng/ml (days 100-110). No increase in mean T levels between 15 and 100 days was identified, and the onset of puberty was earlier in some males than measured previously in this species.     

Concentrations of testosterone and androsterone in peripheral and umbilical venous plasma of fetal rats

Mean +/- s.d. testosterone concentrations in the peripheral plasma of 21- and 22-day-old male fetuses (1.32 +/- 0.43 ng/ml) were significantly (P less than 0.05) higher than those in the umbilical venous plasma (0.37 +/- 0.08 ng/ml). Testosterone concentrations in umbilical venous plasma of male and female (0.29 +/- 0.06 ng/ml) fetuses and in peripheral plasma of female fetuses (0.36 +/- 0.10 ng/ml) were not significantly different. Androsterone levels measured in umbilical venous plasma of male (11.5 +/- 2.5 ng/ml) and female (12.3 +/- 2.1 ng/ml) fetuses were nearly as high as those in peripheral plasma (males, 12.9 +/- 3.1; females, 13.3 +/- 3.5 ng/ml). There were high concentrations of androsterone in the placentas of male (33 +/- 4 ng/g) and female (33 +/- 5 ng/ml) fetuses, suggesting that this organ is the major source of fetal androsterone. We also conclude that a major part of the testosterone present in female fetuses is secreted by the placentas.     

Hormonal changes during puberty. IV. Longitudinal study of acrenal androgen secretions.

Longitudinal studies of plasma dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA) were made in 13 girls aged 7 years and 14 aged 10 years, during 3 years, at 6-month intervals. Similarly, two groups of 12 boys aged 8 years and 11 years were followed. In addition, 3 girls with premature adrenarche and 4 male patients with Addison's disease were studied. In the normal girls a significant rise of plasma DHEA-S and DHEA occurred from 6 years of bone age (51.4 +/- 9.0 ng/ml and 50.5 +/-9.2 ng/100 ml, respectively) to 8 years (119. 7 +/- 19.1 ng/ml and 94.5 +/- 16.5 ng/100 ml). A further significant rise was apparent at 11 years (385.8 +/-60.9 ng/ml) and 329.0 +/- 78.4 ng/100 ml). In boys, a similar rise of DHEA-S and DHEA was observed between 6 years of bone age (75.8 %/- 12 ng/ml and 44.3 +/- 7.6 ng/100 ml) and 8 years (157.4 +/- 28.9 ng/ml and 76.1 +/- 8.9 ng/100 ml). Furhter significant rise of DHEA-S and DHEA were seen at 13 years of bone age (563.7 +/- 123.7 ng/ml and 267.9 +/- 50.0 ng/100 ml, respectively). Testosterone in both sexes rose 2-3 years later than DHEA-S and DHEA. In female patients with premature adrenarche, higher plasma levels of DHEA-S and DHEA were found when compared to normal levels at similar chronological and bone ages. Very low plasma concentrations of DHEA-S and DHEA were obsrved in the patients with Addison's disease.     

Measurement of 5-androsten-3beta,17beta-diol in spermatic and peripheral venous blood samples from the same human subjects by a radioimmunoassay method

An original method for 5-androsten-3beta,17beta-diol (A-diol) measurement using an antiserum against A-diol-16-CMO-BSA is described. A-diol and testosterone (T) were determined by radioimmunoassay methods in spermatic and peripheral venous plasma of nine normal subjects during surgical intervention for inguinal hernia repair. In spermatic venous plasma the levels of T and A-diol were, respectively, 25.9 +/- 13.3 and 4.8 +/- 5.1 microgram/100ml (mean +/- SD) with an A-diol/T ratio of 0.19 +/- 0.15 (mean +/- SD); in peripheral plasma the levels of T and A-diol were, respectively, 269 +/- 58 and 91 +/- 25 ng/100 ml (mean +/- SD) with an A-diol/T ratio of 0.35 +/- 0.12 (mean +/- SD) significantly different from spermatic venous plasma (p less than 0.01). From these data a mean testicular A-diol secretion of about 0.70 mg/24 h can be calculated: this value corresponds approximately to the 50% of the blood production rate (BPR) of this steroid. So it can be assumed that a large amount of A-diol in systemic blood comes from sources outside the male gonad.     

Response of thyrotropin, prolactin and free thyroid hormones to graded exercise in normal male subjects

Serum levels of thyrotrophin (TSH), prolactin (PRL), free thyroxine (FT4) and free triiodothyronine (FT3) were determined before and after physical exercise in 21 normal male subjects. The subjects were divided into 3 groups as follows: group I--light exercise (exercise on the Mijnhardt bicycle ergometer at 100 Watts for 15 min); group II--moderate exercise (a 5 km marathon); group III--heavy exercise (a 10 km marathon). In group I, TSH level rose from 1.96 +/- 0.42 mu u/ml (mean +/- SEM) to 2.52 +/- 0.30 mu u/ml (p less than 0.01), and PRL levels rose from 11.0 +/- 2.0 ng/ml to 19.0 +/- 5.2 ng/ml (p less than 0.01). In group II, TSH rose from 2.11 +/- 0.51 mu u/ml to 2.62 +/- 0.56 mu u/ml (p less than 0.05), and PRL rose from 11.2 +/- 1.6 ng/ml to 24.0 +/- 5.2 ng/ml (p less than 0.01). In group III, TSH rose from 2.01 +/- 0.41 mu u/ml to 2.36 +/- 0.45 mu u/ml (p less than 0.02), and PRL rose from 12.1 +/- 2.0 ng/ml to 47.7 +/- 9.3 ng/ml (p less than 0.01). The serum levels of FT4 showed different results among the three groups: Group I showed an increased response from 1.60 +/- 0.12 ng/dl to 1.72 +/- 0.12 ng/dl (p less than 0.01); Group II showed no significant difference; and group III demonstrated a diminished response from 1.61 +/- 0.14 ng/dl to 1.45 +/- 0.16 ng/dl (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical study on early changes in thyroid function of hyperthyroidism treated with propylthiouracil and a relatively small dose of iodide.

In order to compare the acute effects of three kinds of antithyroid agents of iodide (I-), propylthiouracil (PTU) and PTU combined with iodide (PTU+I-) on thyroid function in hyperthyroid patients with diffuse goiter, serum concentrations of thyroxine (T4), triiodothyronine (T3), T3-resin sponge uptake (T3-RU) and free thyroxine index (FT4I) were employed as thyroid function parameters. In the group given iodine (1 mg/day) as iodinated-lecithine, the initial values of T4, T3, T3-RU and FT4I were 20.9 +/- 1.6 microng/100 ml (T4), greater than 740 ng/100 ml (T3), 49.5 +/- 2.3% (T3-RU) and 14.7 +/- 1.8 (FT4I). At the end of one week of therapy, they decreased clearly to 15.6 +/- 2.2 microng/100 ml, 457 +/- 87 ng/100 ml, 42.2 +/- 4.0% and 9.7 +/- 2.4. The so-called "escape phenomenon" from iodide inhibition was observed in serum T4, T3-RU and FT4I values at the end of two weeks of iodide therapy, while serum T3 continued to decrease but the value of T3 was far outside of the normal range. In the PTU group (300 mg/day), thyroid function parameters were 22.5 +/- 0.8 microng/100 ml (T4), greater than 592 ng/100 ml (T3), 54.9 +/- 1.0% (T3-RU) and 18.7 +/- 1.0 (FT4I) before treatment. They decreased continually week by week. At the end of four-week treatment with PTU, the value of each thyroid function parameter was 11.1 +/- 1.9 microng/100 ml, 229 +/- 56 ng/100 ml, 36.6 +/- 4.4% and 5.7 +/- 1.7. In the group of hyperthyroidism simultaneously given both PTU and iodide (300 mg/PTU and 1 mg/iodine), these thyroid function parameters decreased as well as in the group treated with PTU alone for more than two weeks. More rapid or significant decrease of T4, T3, T3-RU and ft4i in PTU+I- group than in PTU group was observed in the present study. These results suggested strongly that iodide alone was not an adequate therapy for hyperthyroidism as well known and they were also compatible with the idea that the concomitant administration of PTU and iodide was more effective in the early phase of therapy of hyperthyroidism than PTU alone.     

Effects of exogenous TSH on the thyroid activity of adult or neotenic amphibians

In adult Anuran and neotenic Urodela, bred in laboratory conditions, the levels of plasma thyroid hormones are undetectable (T3 less than 50 ng/100 ml, T4 less than 5 ng/100 ml). Thyroid function can be reactivated after ovine TSH treatment. Under those conditions, metamorphosis is induced in the axolotl and T4 plasmatic levels reaches 0,53 +/- 0,13 micrograms/100 ml and those of T3 9 +/- 2,64 ng/100 ml. In adult Anuran, thyroid reactivation under thyrotropic treatment determines an increased secretion of T4 whereas T3 remains below the limits of detection of the assay procedure. This aptitude of adult Anuran thyroid to answer thyrotropic stimulation suggests a cyclic function of the gland after metamorphosis.     

Study of plasma aldosterone in normal pregnancy, in pre-eclamptic women and in cord plasma of newborns.

A radioimmunoassay without chromatography was used for the determination of plasma aldosterone in pregnancy. The mean values (+/- S.D.) of aldosterone concentration increased consistently from 23.2 +/- 5.3 ng/100 ml (n = 14) during the first trimester to 37.2 +/- 10.6 ng/100 ml (n = 17) during the second trimester and 64.0 +/- 18.8 ng/100 ml (n = 29) during the third trimester of pregnancy. The highest values were found at delivery (71.9 +/- 14.2 ng/100 ml; n = 21) and in the cord plasma of newborns (83.4 +/- 14.9 ng/100 ml; n = 21). Significantly lower plasma aldosterone values were found in the plasma of pre-eclamptic women during the third trimester of pregnancy (41.9 +/- 21.3 ng/100 ml; n = 11).     

TBG-dependency of age related variations of thyroxine and triiodothyronine.

Thyroxine (T4), triiodothyronine (T3) and thyroxine-binding globulin (TBG) were determined in healthy individuals ranging in age from newborn to 95 years. T4: 10.25 +/- 1.62 microng/100 ml, T3: 1.62 +/- 0.35 ng/ml and TBG: 1.34 +/- 0.15 mg/100 ml, were found elevated until puberty compared to a middle age group with T4: 7.27 +/- 2.26 microng/100 ml, T3: 1.15 +/- 0.24 ng/ml and TBG: 0.98 +/- 14 mg/100 ml. T4 and T3 followed almost TBG concentration. In old age is dissociation between T4: 5.79 +/- 1.56 microng/100 ml, T3: 0.79 +/- 0.21 ng/ml and TBG: 1.28 +/- 0.15 mg/100 ml was found. Except for old age the ratio T4/TBG and T3/TBG minimized the age dependent variation of T4 and T3 and reduced the coefficient of variance from 26% to 17.7% for T4 and from 26.5 to 25% for T3. Age reduction of T4/TBG is 15% and of T3/TBG 13% respectively more pronounced than for T4 and T3 alone. These data indicate: 1) age related variations of T4 and T3 due to age dependency of TBG, 2) deviation of T4 and T3 values in old age from that expected by their TBG levels and 3) the importance of the routine use of hormone/TBG ratio.     

Clinico-hormonal correlation of oligospermic patients in the below sea level environment (Jordan Valley)

A correlation between serum levels of luteinizing hormone (LH), total testosterone (T), free T and sex-hormone binding globulin (SHBG) in normospermic and in oligospermic male people was done. This study was designed to measure serum levels of these hormones and of SHBG in people living at different altitude environments relative to sea level: at 209-408 meters below (the Jordan Valley, JV) and at 620 meters above (Irbid city, IC). In addition, a clinical awareness study of oligospermia was done in the North of Jordan (IC). Seminal analysis in 287 male people (age range, 18 to 40 years old) during the period between 12/6/1999 and 12/2/2002 showed an oligospermia of 31.4%. Serum levels of LH, total T, free T and SHBG in normospermic subjects in IC were similar to those in normospermic of the JV (3.4 +/- 1.2 vs. 4.0 +/- 1.7 MIU/ml, 19.9 +/- 4.0 vs. 20.4 +/- 5.6 ng/ml, 53.9 +/- 15.6 vs. 47.9 +/- 10.7 pg/ml, 19.5 +/- 3.2 vs. 18.6 +/- 2.16 nmol/l, respectively). Oligospermia was associated with increase in total T at both IC (27.5 +/- 4.6 vs. 19.9 +/- 4.0 ng/ml) and the JV (30.7 +/- 3.4 vs. 20.5 +/- 5.6). The higher serum level of total T in oligospermic people in both IC and the JV was associated with higher levels of SHBG compared to those levels in normospermic subjects. On the other hand, oligospermic subjects have lower serum level of free T than in normospermic males (41.5 +/- 10.0 vs. 53.9 +/- 15.6) only in IC, while in the JV, serum free T level was similar (46.5 +/- 6.1 vs. 47.9 +/- 10.7). Taken together data for both locations, IC and the JV, suggest a clear correlation between total T and SHBG levels in both groups' normospermic and oligospermic subjects.     

Plasma thyroxine and cortisol under basal conditions and during cold stress in the aging dog

The effects of aging on plasma concentration of thyroxine (T4) and cortisol and on responses of these hormones to low ambient temperatures were determined in the dog. Female beagle dogs were divided into three age groups: old, adult, and puppies. The mean (+/- SD) ages were 11.4 +/- 0.2 years, 3.0 +/- 0.4 years, and 7.6 +/- 0.2 weeks, respectively. All dogs came from a genetically homogeneous colony and were free from any disease. The adult and old dogs were used during anestrus. Based on four daily blood samples, the mean (+/- SE) T4 level in the old dogs (2.8 +/- 0.1 microgram/dl) was significantly (P less than 0.001) lower than that in the adults (4.2 +/- 0.2 micrograms/dl) and puppies (4.4 +/- 0.2 micrograms/dl). By contrast, mean plasma cortisol levels in the old dogs (21.1 +/- 3.1 ng/ml) and adults (15.4 +/- 2.4 ng/ml) were significantly higher than those in the puppies (7.2 +/- 1.1 ng/ml). No significant changes in plasma T4 and cortisol occurred in any of the three age groups at 22 degrees C or during exposure to 10 or 4 degrees C. Exposure to -5 degrees C, however, produced significant increases in T4 (greater than 130% by 5 hr) and cortisol (greater than 280% by 1 hr) in adult dogs. This temperature produced only a modest increase in T4 (70% by 3.5 hr) and no change in cortisol in the old dogs. The puppies showed no change in T4 and cortisol during exposure to -5 degrees C. The results demonstrate that with advancing age, plasma T4 and cortisol concentrations change in opposite directions, thus supporting the hypothesis of a negative relationship between these two hormones. These results also show that the responses of these hormones to the stress of cold decline during aging and are not yet developed in the very young.     

Pulsatile nature of luteinizing hormone release is maintained during luteinizing hormone-releasing hormone stimulation in normal male rats

The plasma LH concentration is believed to be reasonably steady in normal male rats. We found that LH is released in a regular pulsatile fashion. The overall mean concentration of plasma LH in normal male rats was 46.6 +/- 4.4 (mean +/- SEM) ng/ml. The normal male rats showed periodic LH pulses: the mean pulse amplitude was 144.4 +/- 25.5 ng/ml and the inter-peak interval was 22.5 +/- 2.0 min. Each pulse lasted 9.7 +/- 0.8 min. When LH-RH (1 microgram/kg) was injected as a bolus, the peak concentration was attained in 10-30 min reaching a peak concentration of 279.4 +/- 39.6 ng/ml. Distinct pulsatile bursts of plasma LH were discernible during the period of elevated plasma LH concentration. When a higher dose of LH-RH (5 micrograms/kg) was administered, the LH concentration slowly increased to a peak concentration of 400.2 +/- 38.7 ng/ml in 20-40 min. The pulsatile nature of the LH concentration was recognizable with distinct bursts. We have observed that: (a) normal male rats release LH in a pulsatile fashion with an approximate 20-min inter-peak interval; (b) mean LH pulses last less than 10 min, and (c) the LH pulses are visible even with elevated LH and LH-RH concentrations in the general circulation.     

Dynamics of circulating osteocalcin in rats during growth and under experimental conditions.

Osteocalcin is the most abundant non-collagenous protein produced in the process of bone formation. A specific radioimmunoassay has been developed using a rabbit antiserum raised against osteocalcin extracted from rat bone. The sensitivity of the assay was tested in male and female rats under different experimental conditions: ovariectomy led to a mild increase in circulating osteocalcin (70.6 +/- 6.9 vs 51.6 +/- 6.3 ng/ml; p < 0.05) and deprivation of dietary calcium elevated plasma levels further (119 +/- 6.3 ng/ml; p < 0.01). As expected, pharmacological enhancement of bone turnover with calcitriol produced a significant increase in plasma osteocalcin (296 +/- 24.1 vs 89.5 +/- 5.1 ng/ml; p < 0.01), whereas prednisolone, a steroidal compound known to inhibit osteoid mineralization, significantly reduced circulating concentrations of this protein (70 +/- 7.4 vs 100 +/- 6.3 ng/ml; p < 0.05). Plasma kinetics recorded in female rats between birth and the 100th week revealed a highly significant (p < 0.001) elevation peaking at the third week (231 +/- 70.6 ng/ml) and slowly declining to reach values measured at birth (41.3 +/- 9.2 ng/ml) at the 16th week (47 +/- 4.6 ng/ml). Subsequently, a small but significant (p < 0.05) decline towards senescence was recorded. The osteocalcin surge preceded the period of rapid growth (weeks 3 to 11) estimated by vertebral length progression, showing a tendency to stabilize as growth spurt slowed down. A moderate but significant (p < 0.01) increment was observed after mating (87.8 +/- 5.1 vs 69.5 +/- 4.0 ng/ml). Although plasma osteocalcin remained stable during lactation, average levels were elevated in comparison with age-matched non-pregnant controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Social suppression of ovarian cyclicity in captive and wild colonies of naked mole-rats, Heterocephalus glaber

To investigate the endocrine cause of reproductive suppression in nonbreeding female naked mole-rats, animals from 35 colonies were studied in captivity. Urinary and plasma progesterone concentrations were elevated in pregnant females (urine: 10.0-148.4 ng/mg Cr, 27 samples from 8 females; plasma: 3.6-30.0 ng/ml, 5 samples from 5 females; Days 21-40 of pregnancy) and cyclic breeding females (urine: 0.5-97.8 ng/mg Cr, 146 samples from 7 females; plasma: less than 1.0-35.4 ng/ml, 25 samples from 7 females). The latter group showed cyclic patterns of urinary progesterone, indicating a mean ovarian cycle length of 34.4 +/- 1.6 days (mean +/- s.e.m.) with a follicular phase of 6.0 +/- 0.6 days and a luteal phase of 27.5 +/- 1.3 days (19 cycles from 9 breeding females). In non-breeding females urinary and plasma progesterone values were undetectable (urine: less than 0.5 ng/mg Cr, 232 samples from 64 females; plasma: less than 1.0 ng/ml, 7 samples from 6 females). Breeding females had higher (P less than 0.001) plasma LH concentrations (3.0 +/- 0.2 mi.u./ml, 73 samples from 24 females) than did non-breeding females (1.6 +/- 0.1 mi.u./ml, 57 samples from 44 females). Urinary and plasma progesterone concentrations in non-breeding females from wild colonies situated near Mtito Andei, Kenya, were either below the assay sensitivity limit (urine: less than 0.5 ng/mg Cr, 11 females from 2 colonies; plasma: less than 1.0 ng/ml, 25 females from 4 colonies), or very low (plasma: 1.6 +/- 0.6 ng/ml, 15 females from 4 colonies). In captivity, non-breeding females removed from their colonies (i.e. the dominant breeding female) and either paired directly with a non-breeding male (N = 2), or removed and housed singly for 6 weeks before pairing with a non-breeding male (N = 5) may develop a perforate vagina for the first time in as little as 7 days. Urinary progesterone concentrations rose above 2.0 ng/mg Cr (indicative of a luteal phase) for the first time 8.0 +/- 1.9 days after being separated. These results suggest that ovulation is suppressed in subordinate non-breeding female naked mole-rats in captive and wild colonies, and show that plasma LH concentrations are significantly lower in these non-breeding females. This reproductive block in non-breeding females is readily reversible if the social factors suppressing reproduction are removed.     

A simple technique for collecting blood of testicular origin: application to in vivo studies on testicular steroidogenesis in rats and Macaca fascicularis

A technique for rapidly collecting blood of testicular origin is described, one which can provide sufficient plasma amounts to investigate some steps of testicular steroid biogenesis in vivo in 2 species. In adult male rats, testosterone (T), androstenedione (4A) and 5-androstenediol (5AD) were determined in pampiniform plexus testicular venous blood (PPTV) and peripheral (PV) blood samples before and 2 h after human Chorionic Gonadotropin (hCG). PPTV concentration of 5AD was 0.83 +/- 0.1 ng/ml (mean +/- SEM) with a PPTV/PV ratio of 7.0 +/- 1.0, comparable to a PPTV/PV ratio for 4A of 5.8 +/- 1.8. After hCG, PPTV concentration of 5AD significantly increased to 1.28 +/- 0.15 ng/ml (P less than 0.05). Those data are in favor of a participation of 5-ene pathway to testicular biogenesis of T associated to a 4-ene pathway which is predominant. In adult male Macaca fascicularis, spermatic vein (SV) concentrations of 5AD and 4A were comparable (3.0 +/- 1.2 vs 4.3 +/- 1.0 ng/ml) as well as SV/PV ratios under basal conditions (3.5 +/- 0.9 vs 5.1 +/- 0.1), as well as 48 h after hCG, confirming in vivo that both 5-ene and 4-ene pathways are involved in testicular T biogenesis. Testicular production of estradiol (E2), estrone (E1) and their sulfates E2S and E1S showed a SV/PV ratio significantly higher than 1 (3.4 +/- 0.6; 2.4 +/- 0.1; 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively).     

The role of circulating ghrelin in growth hormone (GH) secretion in freely moving male rats

To examine the physiological significance of plasma ghrelin in generating pulsatile growth hormone (GH) secretion in rats, plasma GH and ghrelin levels were determined in freely moving male rats. Plasma GH was pulsatilely secreted as reported previously. Plasma ghrelin levels were measured by both N-RIA recognizing the active form of ghrelin and C-RIA determining total amount of ghrelin. Mean +/- SE plasma ghrelin levels determined by N-RIA and C-RIA were 21.6 +/- 8.5 and 315.5 +/- 67.5 pM, respectively, during peak periods when plasma GH levels were greater than 100 ng / ml. During trough periods when plasma GH levels were less than 10 ng / ml, they were 16.5 +/- 4.5 and 342.1 +/- 29.8 pM, respectively. There were no significant differences in plasma ghrelin levels between two periods. Next, effect of a GH secretagogue antagonist, [D-Lys-3]-GHRP-6, on plasma GH profiles was examined. There were no significant differences in both peak GH levels and area under the curves of GH (AUCs) between [D-Lys-3]-GHRP-6-treated and control rats. These findings suggest circulating ghrelin in peripheral blood does not play a role in generating pulsatile GH secretion in freely moving male rats.     

Testosterone modulates the differential release of luteinizing hormone and follicle-stimulating hormone that occurs in response to changing gonadotropin-releasing hormone pulse frequency in the male monkey, Macaca fascicularis

Selective elevations of plasma follicle-stimulating hormone (FSH) levels are characteristic of some physiological conditions, such as the early stages of human puberty, and in some disorders of testicular function, such as idiopathic oligospermia. We tested the hypotheses that a slow gonadotropin-releasing hormone (GnRH) pulse frequency favors a selective elevation of plasma FSH and that this is influenced by the circulating steroidal milieu. We administered exogenous GnRH at frequencies of once every 90 min (q 90 min) and once every 240 min (q 240 min) to castrated prepubertal male monkeys who had received either empty (sham) or testosterone (T)-filled Silastic capsules at the time of castration. At the end of each experimental frequency period, mean plasma levels of luteinizing hormone (LH) and FSH were measured. Plasma T levels were also measured. Animals with T implants had plasma levels of this hormone that were in the adult range (approximately equal to 8 ng/ml), whereas those with sham implants had plasma T levels in the prepubertal range (less than or equal to 4 ng/ml). In animals with sham implants, mean plasma FSH levels were markedly elevated at the slower GnRH pulse frequency (39.5 +/- 3.6 ng/ml following GnRH q 240 min compared with 23.7 +/- 2.8 ng/ml following GnRH q 90 min). This selective FSH elevation was not apparent in animals with T implants. Mean plasma LH levels were similar (approximately equal to 8 micrograms/ml) at the two GnRH pulse frequencies, in both T-treated and sham-implanted animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma FSH and LH in prepubertal Booroola ewe lambs

Basal plasma concentrations (four 30-min samples) and GnRH-induced release of gonadotrophins were measured every 15 days between 30 and 90 days and at 110 days of age in Merino ewe lambs from the prolific Booroola ('B') flock (n = 18-23), the medium prolificacy ('T') flock (n = 14-20), and the 'O' flock (n = 4-8) of low prolificacy. At ages of 30 and 45 days B ewe lambs had mean basal plasma FSH concentrations of 145 and 122 ng/ml which were significantly higher (P less than 0.01) than those seen in T (45 and 53 ng/ml), and O (39 and 38 ng/ml) flock ewes. Between 60 and 110 days of age there were no significant differences between genotypes. The increment in FSH concentrations above basal levels induced by the subcutaneous injection of 100 micrograms synthetic GnRH was only significantly (P less than 0.05) greater in B than T and O genotype ewe lambs at 110 days of age but not at other ages. The basal plasma FSH differences between the B, T and O genotypes at 30 and 45 days of age were not consistently related to the size of litter in which lambs were born. At 30 days of age the mean plasma LH concentration of B, T, and O flock lambs were 2.6 +/- 0.5, 1.2 +/- 0.6 and 0.7 +/- 0.8 ng/ml respectively. These differences were not significant. At later ages there were also no significant differences between the genotypes with respect to basal LH, and the increase in LH induced by exogenous GnRH was always similar for the three genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uptake and effect of praziquantel and the major human oxidative metabolite, 4-hydroxypraziquantel, by Schistosoma japonicum

After exposure to praziquantel in vitro at a concentration of 1 microgram/ml for 0.5-2 hr, amounts of praziquantel in Schistosoma japonicum varied from 2.1 +/- 1.2 to 3.7 +/- 1.6 ng/male worm and 1.3 +/- 1.2 to 2.2 +/- 1.5 ng/female worm during the time studied. At 30 micrograms/ml, praziquantel amounts were 11-33-fold higher. However, within 2 hr after removal from a medium containing 30 micrograms/ml praziquantel, 95% of the drug was released from the parasites. When S. japonicum worm pairs were incubated in vitro with 1, 10, and 30 micrograms/ml of 4-hydroxypraziquantel, the major human oxidative metabolite of praziquantel, 0.2 +/- 0.2, 3.8 +/- 1.3, and 7.4 +/- 1.3 ng/worm pair, respectively, were found after a 2-hr incubation. 15-30-fold lower than corresponding worm pair amounts of praziquantel. In vivo, when 4- or 5-wk S. japonicum-infected mice were treated orally with praziquantel (300 mg/kg), peak concentrations of praziquantel in plasma determined by high pressure liquid chromatography were 14.7 +/- 1.5 micrograms/ml (4-wk infection) and 16.7 +/- 2.8 micrograms/ml (5-wk infection) 15 min after treatment. Corresponding in vivo worm praziquantel amounts were 1.8 +/- 0.4 ng/male worm and 2.4 +/- 1.1 ng/female worm, respectively, in the 4-wk infection and 4.6 +/- 1.6 ng/male worm and 5.6 +/- 1.2 ng/female worm in the 5-wk infection. Peak plasma concentrations of 4-hydroxypraziquantel were similar but corresponding in vivo worm amounts were 1-20-fold lower, depending on the time after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)