Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired LH-RH release by estrogen in women with sulpiride-induced hyperprolactinemia

The effects of hyperprolactinemia on the release of immunoreactive luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH) in response to iv injection of 20 mg conjugated estrogens (Premarin) were studied. Five normal cycling women were injected with Premarin on the morning of the 7th day of the first cycle (control cycle), and then the plasma levels of LH-RH, LH, and prolactin (PRL) were determined every 8 to 16 hours for 72 h. Two months later, the same women received 200 mg of oral sulpiride daily for 8 days from the 3rd day of the cycle (sulpiride treated cycle), and then the same protocol as in the control cycle was applied. Mean (+/- SE) plasma levels of PRL on day 7 in the sulpiride treated cycle were significantly higher than those in the control cycle (118 +/- 24 ng/ml vs. 14 +/- 4 ng/ml, p less than 0.001). After estrogen injection, the mean percent increases in immunoreactive LH-RH at 32 h (control: 71 +/- 38% vs. sulpiride: 6 +/- 36%) and 40 h (154 +/- 38% vs. -5 +/- 21%) and in LH at the 48 h (175 +/- 89% vs. 57 +/- 57%) and 56 h (99 +/- 32% vs. 7 +/- 21%) were significantly (p less than 0.01 or p less than 0.05) suppressed in the sulpiride cycle. These data suggest that the impaired positive feedback effect of estrogen on LH-release in hyperprolactinemic anovulatory women may be caused, at least in part, by disturbed LH-RH release.     

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Estrone sulfate, estrone and estradiol concentrations in normal and cirrhotic postmenopausal women

Circulating levels (mean +/- SD) of estrone sulfate (E1S), estrone (E1) and estradiol-17 beta (E2) were measured in normal and cirrhotic postmenopausal women matched for body weight and age. In cirrhotic postmenopausal women, the E1S concentrations (201 +/- 46 pg/ml), while both E1 and E2 levels showed an increase (46 +/- 7 and 30 +/- 8 pg/ml) compared to control subjects (32 +/- 6 and 18 +/- 7 pg/ml). These data suggest that the liver plays an important role on the control of estrogen sulfation.     

Decreased pulsatile LH secretion in heifers superovulated with eCG or FSH

This study was designed to test the hypothesis that treatment with super-ovulatory drugs suppresses endogenous pulsatile LH secretion. Heifers (n=5/group) were superovulated with eCG (2500 IU) or FSH (equivalent to 400 mg NIH-FSH-P1), starting on Day 10 of the estrous cycle, and were injected with prostaglandin F(2alpha) on Day 12 to induce luteolysis. Control cows were injected only with prostaglandin. Frequent blood samples were taken during luteolysis (6 to 14 h after PG administration) for assay of plasma LH, estradiol, progesterone, testosterone and androstenedione. The LH pulse frequency in eCG-treated cows was significantly lower than that in control cows (2.4 +/- 0.4 & 6.4 +/- 0.4 pulses/8 h, respectively; P<0.05), and plasma progesterone (3.4 +/- 0.4 vs 1.8 +/- 0.1 ng/ml, for treated and control heifers, respectively; P<0.05) and estradiol concentrations (25.9 +/- 4.3 & 4.3 +/- 0.4 pg/ml, for treated and control heifers, respectively; P<0.05) were higher compared with those of the controls. No LH pulses were detected in FSH-treated cows, and mean LH concentrations were significantly lower than those in the controls (0.3 +/- 0.1 & 0.8 +/- 0.1, respectively; P<0.05). This suppression of LH was associated with an increase in estradiol (9.5 +/- 1.4 pg/ml; P<0.05 compared with controls) but not in progesterone concentrations (2.1 +/- 0.2 ng/ml; P>0.05 compared to controls). Both superovulatory protocols increased the ovulation rate (21.6 +/- 3.9 and 23.0 +/- 4.2, for eCG and FSH groups, respectively; P>0.05). These data demonstrate that super-ovulatory treatments decrease LH pulse frequency during the follicular phase of the treatment cycle. This could be explained by increased steroid secretion in the eCG-trated heifers but not in FSH-treated animals.     

The effect of weight loss on serum concentrations of FAS and tumour necrosis factor alpha in obese women

INTRODUCTION: Apoptosis can influence both adipose tissue mass and its distribution. The suprafamily of tumour necrosis factor (TNF) receptors stimulate apoptosis. The aim of the study was to assess serum concentrations of tumour necrosis factor alpha (TNF-alpha), TNF soluble receptors (sTNFRs) and FAS in obese subjects and to examine the changes in these parameters after weight loss. MATERIAL AND METHODS: The study group consisted of 23 obese women without additional disease aged 36.6 +/- 10.9 years. These were examined before and after three-month weight reduction treatment consisting of a diet of 1000 kcal/day and physical exercise. The control group comprised 17 lean healthy women aged 40.3 +/- 5.5 years. Blood samples were taken in the morning after an overnight fast. Serum concentrations of TNF-alpha, sTNFRs and FAS were measured by enzyme linked immunosorbent assay (ELISA). Serum concentrations of insulin were measured by RIA. Serum concentrations of glucose, total cholesterol, HDL cholesterol and triglycerides were measured by an enzymatic procedure. RESULTS: The mean weight loss over the three-month treatment was 11.4 +/- 3.1 kg. Following weight loss, serum TNF-alpha concentrations decreased significantly (7.3 +/- 3.0 vs. 5.4 +/- 1.6 pg/ml; p < 0.005) and concentrations of sTNFRs increased significantly (1222.6 +/- 211.8 vs. 1325.6 +/- 261.6 pg/ml; p < 0.05 and 1881.5 +/- 337.2 vs. 2057.4 +/- 358.7 pg/ml; p < 0.05 respectively). However, no changes in serum concentrations of FAS were observed after weight loss. CONCLUSION: We observed increased serum concentrations of TNF-alpha but not of FAS in obese women. The concentrations of TNF decreased and those of sTNFRs increased after weight loss. However, the weight reduction therapy did not change serum concentrations of FAS.     

LH release and luteal function in post-partum acyclic ewes after the pulsatile administration of LH-RH

The administration of LH-RH in a pulsatile regimen (100 ng i.v./h for 48 h) to acyclic ewes 26-30 days post partum increased plasma LH concentrations, and both the frequency and amplitude of plasma LH pulses. In 12/14 ewes these increases were followed by plasma LH surges similar to the preovulatory surges observed in 10 control cyclic ewes. Subsequent luteal function in the post-partum ewes was deficient. Plasma progesterone was detected in 7/12 post-partum ewes showing plasma LH surges. The concentrations were lower (1.3 +/- 0.2 ng/ml) and detected for shorter periods (3-10 days) than in cyclic ewes (2.4 +/- 0.2 ng/ml, 12/15 days). In the post-partum ewes the increases in plasma LH concentrations before the LH surge were higher but of shorter duration than in the cyclic ewes. The inadequate luteal function in the post-partum ewes could therefore have been due to inappropriate LH stimulation of the ovary before the LH surge.     

Ghrelin is present in human colostrum, transitional and mature milk

Ghrelin and its mRNA have recently been found in numerous human tissues including breast. The aim of this study was to compare the ghrelin levels in colostrum, mature and transitional milk and plasma in lactating women with plasma samples from non-lactating women. Venous blood samples were obtained from 17 healthy lactating women aged 22-35 years and from 16 age-matched controls. Colostrum, transitional and mature milk samples were collected just before suckling. The level of bioactive ghrelin was determined by RIA. Comparison of ghrelin values for lactating women showed significantly lower concentrations in colostrum (70.3 +/- 18 pg/ml), transitional milk (83.8 +/- 18pg/ml) and mature milk (97.3 +/- 13 pg/ml) than in the corresponding plasma samples (first day 95 +/- 16 pg/ml, 10th day 111 +/- 13 pg/ml and 15th day 135 +/- 16 pg/ml). The plasma concentrations were lower in the lactating than in the non-lactating women. Thus, the ghrelin levels in colostrum, transitional and mature milk were elavated concomitantly with increasing plasma ghrelin after delivery. The origin of milk ghrelin is not known, but it probably comes from the plasma.     

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.     

Lipid peroxidation at various estradiol concentrations in human circulation during ovarian stimulation with exogenous gonadotropins.

The aim of our study was to investigate the correlation between serum malondialdehyde levels and serum estradiol concentrations in healthy human female subjects. Nine hundred and fifty-five blood samples, from infertile women undergoing controlled ovarian hyperstimulation treatment with recombinant follicle-stimulating hormone, were collected for estradiol and malondialdehyde measurements. Five groups were formed according to serum estradiol levels: Group I (< 50 pg/ml), group II (50 - 299 pg/ml), group III (300-999 pg/ml), group IV (1000-1999 pg/ml) and group V (> or = 2000 pg/ml). One-way analysis of variance was used for comparisons. Mean malondialdehyde concentrations were 1.74 +/- 0.24 mmol/ml (group I), 1.53 +/- 0.20 mmol/ml (group II), 1.69 +/- 0.24 mmol/ml (group III), 1.77 +/- 0.21 mmol/ml (group IV) and 1.86 +/- 0.20 mmol/ml (group V), respectively. Mean serum malondialdehyde level at physiological estradiol concentrations (50-199 pg/ml, group II) was significantly (p < 0.01) lower than the mean malondialdehyde levels in other groups. Mean malondialdehyde concentrations among the remaining groups did not significantly differ. Our findings suggest that in vivo lipid peroxidation might be increased when circulating estradiol concentrations are below (< 50 pg/ml) or above (> 300 pg/ml) the physiological limits. High blood estradiol levels in human female subjects during ovarian stimulation with exogenous gonadotropins could be associated with increased serum malondialdehyde concentrations.     

Serum profiles of androstenedione, testosterone and LH from birth through puberty in buffalo bull calves

Blood samples were taken once per week for 4-7 weeks from 59 buffalo calves in 14 age groups, 1-2 months apart. Hormones were quantified by validated radioimmunoassays. Values of androstenedione and testosterone were low at birth (141.3 +/- 33.5 pg/ml and 18.0 +/- 2.9 pg/ml, respectively; mean +/- s.d.). Serum androstenedione concentrations gradually increased from birth until 8 months of age and declined (P less than 0.05) thereafter, whereas mean testosterone values were low up to 8 months and then significantly (P less than 0.05) increased as age advanced. LH concentrations averaged 2.12 +/- 0.47 ng/ml at birth. Thereafter, a decline in LH values was followed by an increase between 6 and 15 months of age. We conclude that, in buffalo bull calves, the pubertal period occurs from about 8 to 15 months of age. For pubertal buffalo bulls 15-17 months of age, serum concentrations of androstenedione, testosterone and LH were 156.9 +/- 54.6 pg/ml, 208.4 +/- 93.8 pg/ml and 2.10 +/- 0.70 ng/ml, respectively.     

Characterization of obese women with reduced sex hormone-binding globulin concentrations

Factors influencing sex-hormone binding globulin (SHBG) concentrations in obesity are poorly understood. Preliminary observations suggest that dietary lipids may be involved and there are data confirming a direct inhibiting effect of insulin. Since only some obese subjects show lowered SHBG levels, we performed this study with the aim of defining obese women with low SHBG (LSO) (2 SD above normal values) in comparison with those presenting normal globulin concentrations (NSO). These groups were selected from a larger group of obese women with a history of normal menses and aged less than 40 years. An age-matched group of normal weight healthy women served as controls. Both LSO and NSO had similar body mass index and percentage body fat, but the waist to hip girth ratio (WHR), an index of body fat distribution, was significantly higher in LSO (0.88 +/- 0.04) than in NSO (0.81 +/- 0.09; P less than 0.05). Gonadotropin and androgen concentrations were similar in both groups, whereas estrone (E1) levels were higher in LSO (32.8 +/- 15.8 pg/ml) than in NSO (19.4 +/- 6.2 pg/ml; P less than 0.05; controls: 23.5 +/- 7.8 pg/ml; P less than 0.05). Moreover, compared to NSO, LSO women had significantly higher glucose-stimulated insulin and C-peptide levels. Partial regression analysis revealed significant correlation coefficients between SHBG, stimulated insulin values (r = -0.38; P less than 0.05) and WHR (r = 0.40; P less than 0.005). Therefore, compared to NSO, LSO women have distinctive clinical and endocrine characteristics, namely more pronounced hyperinsulinemia, higher E1 concentrations and a central type body fat distribution.     

Endometrial tissue and plasma concentrations of 5-androstene-3 beta, 17 beta-diol during the menstrual cycle in normal premenopausal and perimenopausal women

A radioimmunoassay for 5-androstene-3 beta, 17 beta-diol (ADIOL) in human endometrium and plasma is described. The recognised criteria of reliability have been fulfilled. Plasma and endometrial tissue concentrations of ADIOL were determined in samples obtained from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different phases of the menstrual cycle. In perimenopausal women plasma concentrations of ADIOL did not vary throughout the cycle (proliferative phase: 411 +/- 95 (SEM) pg/ml; secretory phase: 462 +/- 28.5 (SEM) pg/ml). For the premenopausal group the pattern was similar (proliferative phase: 568.4 +/- 56.9 (SEM) pg/ml; secretory phase: 663.1 +/- 64.7 (SEM) pg/ml) although a significant difference (P less than 0.05) was noted between late proliferative and late secretory phase levels in these women. A different pattern was observed for endometrial tissue concentrations of ADIOL. In both groups of women a significant (3-4-fold) increase occurred during the secretory phase. There was no apparent relationship between plasma and tissue concentrations of ADIOL either during the proliferative or the secretory phase. There was, however, an age associated decrease for both tissue and plasma ADIOL. Theories are proposed to account for the increase in ADIOL concentration during the luteal phase.     

Self-priming effect of LH-RH on pituitary gonadotropins in hyperprolactinemic women

To investigate how various concentrations of serum prolactin (PRL) influence the priming effect of luteinizing hormone releasing hormone (LH-RH) on the pituitary gland, 24 women with various blood PRL concentrations received intravenous injections of 100 micrograms of synthetic LH-RH twice at an interval of 60 minutes and their serum LH and follicle-stimulating hormone (FSH) were measured and analysed. In the follicular phase with a normal PRL concentration (PRL less than 20 ng/ml, n = 6), marked first peaks of the two hormones following the first LH-RH stimulation and enhanced second peaks after the second LH-RH administration were observed, indicating a typical priming effect of LH-RH on gonadotropins, though the second response of FSH was more moderate than that of LH. In hyperprolactinemia, in which the serum PRL concentration was higher than 70 ng/ml (n = 13), the basal concentration of gonadotropins was not significantly changed but the priming effect of LH-RH on LH and FSH was significantly decreased (p less than 0.01). No marked second peaks of LH and FSH were observed, suggesting an inhibitory effect of hyperprolactinemia on the second release of LH and FSH. In contrast, this effect was restored in a group of women whose serum PRL concentration was between 30 and 50 ng/ml (n = 5). Furthermore, enhanced second peaks of both LH and FSH were noted after successful bromocriptine therapy reduced hyperprolactinemia (PRL greater than 70 ng/ml) to less than 25 ng/ml (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Biological effects of hormone replacement therapy in relation to serum estradiol levels

OBJECTIVE: Tissues in various parts of the body have different sensitivities to estradiol. However, it is very difficult to measure the serum estradiol levels precisely in women receiving oral conjugated equine estrogen, which is a mixture of estrogens. In the present study, we precisely measured the serum levels of estradiol in postmenopausal women undergoing hormone replacement therapy (HRT), and we clarified the relationships between serum estradiol levels and the effects of HRT on the Kupperman index, bone mineral density (BMD), serum gonadotropin, lipid metabolism and unscheduled bleeding as the clinical endpoints. METHODS: Sixty-eight postmenopausal or bilaterally ovariectomized women, aged 30-64 years, who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly assigned to two groups: one group of 34 patients who received oral administration of 0.625 mg conjugated equine estrogen (CEE, Premarin, Wyeth) and 2.5 mg medroxyprogesterone acetate (MPA, Provera, Upjohn) every other day, and another group of 34 patients who received oral administration of 0.625 mg CEE and 2.5 mg MPA every day. All subjects were re-classified into three groups according to the serum estradiol level after 12 months of treatment: (1) low estradiol group (<15 pg/ml, n = 25); (2) middle estradiol group (> or =15 and <25 pg/ml, n = 27), and (3) high estradiol group (> or =25 pg/ml, n = 16). We examined the relationships between serum estradiol level and the effects of estradiol on the Kupperman index, BMD, serum gonadotropin levels, lipid profile and unscheduled bleeding in these three groups. Results: Results obtained by using our newly developed high-performance liquid chromatography (HPLC)-radioimmunoassay (RIA) system clearly showed that the effects on each tissue in postmenopausal women receiving oral CEE and MPA is closely related to estradiol level. The effects of HRT on BMD, serum gonadotropin levels and lipid profile were shown to be clearly dependent on the serum estradiol levels, while the effect of HRT on the Kupperman index was independent of the serum estradiol level. Furthermore, it was also found that a very low concentration of estradiol (<15 pg/ml) was sufficient to suppress the serum LH and FSH levels and to relieve vasomotor symptoms, and that the minimum concentration of estradiol required to increase BMD was 15 pg/ml. On the other hand, the level of estradiol required to reduce total cholesterol, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo B) was found to be more than 25 pg/ml, while the level required to increase high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) was at least 15 pg/ml. The incidence of unscheduled bleeding was also lower in the low estradiol group than in the other estradiol level groups. CONCLUSION: These results suggest that the different clinical endpoints have different response thresholds and thus reflect tissue sensitivity to estradiol levels achieved by HRT.     

Augmentation, by naloxone, of the frequency and amplitude of LH-RH pulses in hypothalamo-hypophyseal portal blood in the castrated ram

The effect of naloxone administration on the LH-RH secretion in hypophyseal portal blood and LH secretion in peripheral blood was studied in four short term castrated rams (between 2 to 4 days after castration). For two animals (A and B) given a single naloxone injection, an increase of LH-RH pulse amplitude was observed (A, 22.3 to 80.5 pg/ml and B, 22.5 to 34.5 pg/ml) with only a small (nonsignificant) increase in LH-RH pulse frequency. For animals C and D given four injections of naloxone, both LH-RH pulse amplitudes and LH-RH pulse frequency were increased. Means of LH-RH pulse amplitude increase from 29.3 to 65.1 pg/ml and from 34.6 to 50.8 pg/ml for animals C and D respectively and the number of LH-RH pulses detected during the 3 hrs. before and after the first injection of naloxone were respectively 3 vs. 5 and 3 vs. 7. Whereas all LH pulses were preceded with a LH-RH pulse in animals A and B, after the multiple naloxone injections in animals C and D, a rapid LH-RH pulse frequency was associated with a sustained increment of LH secretion in peripheral blood in such a way that individual LH pulses were not clearly defined. The present report is the first documentation on naloxone increasing the release of LH-RH secretion in hypophyseal portal blood of conscious, unrestrained, short-term castrated rams. The results indicate: (1) that the opiate antagonist naloxone is able to increase both the amplitude and the frequency of LH-RH discharge by the hypothalamus and (2), when the LH-RH pulse frequency exceeds one pulse every 30 min., discrete LH secretory episodes are not observed in peripheral blood.     

Immunoreactive LHRH in cerebrospinal fluid: the clinical significance in intracranial diseases

Cerebrospinal fluid (CSF) and plasma levels of luteinizing hormone-releasing hormone (LHRH) were measured by RIA in 46 patients with acute intracranial diseases, ie, cerebral bleeding (group A), cerebral thrombosis (B), head injury (C) and meningitis (D), and the results were compared to those obtained in 21 patients with non-intracranial diseases (group E; control). Immunoreactive LHRH concentrations in CSF (CSF IR-LHRH) of 8 postmenopausal women in group E ranged 1.3 to 6.1 (mean +/- SE: 3.1 +/- 0.6) pg/ml, and those of 5 other women and 8 men with group E ranged 1.0 to 5.6 (3.6 +/- 0.4)pg/ml. In 7 out of 15 patients in group A(7/15), CSF IR-LHRH were above the levels seen in group E. In group B, C and D, CSF IR-LHRH were above the control levels in 9/15, 1/9, 3/7, respectively. The changes in plasma LHRH were not clear in postmenopausal patients in groups A and B. Plasma IR-LHRH in other women and men in group A were above the control levels in 2 out of 9 patients (2/9). Those in groups B, C and D were above the control levels in 3/8, 1/9, 2/7, respectively. Moreover, both plasma and CSF IR-LHRH of 13 patients in group A or B in chronic stage were within the control ranges. In cases observed following the time course, the occasionally increased IR-LHRH in plasma and CSF tended to decrease following the abatement of the diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.     

Relationship between the preovulatory luteinizing hormone (LH) surge and androstenedione synthesis of preantral follicles in the cyclic hamster: detection by in vitro responses to LH

Preantral follicles of cyclic hamsters were isolated on proestrus, estrus and diestrus I, incubated for 3 h in 1 ml TC-199 containing 1 microgram ovine luteinizing hormone (LH) (NIH-S22), and the concentrations of progesterone (P), androstenedione (A) and estradiol (E2) determined by radioimmunoassay. At 0900-1000 h on proestrus (pre-LH surge) preantral follicles produced 2.4 +/- 0.3 ng A/follicle per 3 h, less than 100 pg E2/follicle and less than 250 pg P/follicle. At the peak of the LH surge (1500-1600 h) preantral follicles produced 1.8 +/- 0.2 ng P and 1.9 +/- 0.1 A and less than 100 pg E2/follicle. After the LH surge (1900-2000 h proestrus and 0900-1000 h estrus) preantral follicles were unable to produce A and E2 but produced 4.0 +/- 1.0 and 5.0 +/- 1.1 ng P/follicle, respectively. By 1500-1600 h estrus, the follicles produced 8.1 +/- 3.1 ng P/follicle but synthesized A (1.6 +/- 0.2 ng/follicle) and E2 (362 +/- 98 pg/follicle). On diestrus 1 (0900-1000 h), the large preantral-early antral follicles produced 1.9 +/- 0.3 ng A, 2.4 +/- 0.4 ng E2 and 0.7 +/- 0.2 ng P/follicle. Thus, there was a shift in steroidogenesis by preantral follicles from A to P coincident with the LH surge; then, a shift from P to A to E2 after the LH surge. The LH/follicle-stimulating hormone (FSH) surges were blocked by administration of 6.5 mg phenobarbital (PB)/100 g BW at 1300 h proestrus. On Day 1 of delay (0900-1000 h) these follicles produced large quantities of A (2.2 +/- 0.2 ng/follicle) and small amounts of E2 (273 +/- 27 pg/follicle) but not P (less than 250 pg/follicle).(ABSTRACT TRUNCATED AT 250 WORDS)