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G A Laughlin

Publications and source records attributed to G A Laughlin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism.

Recently, we reported that hyperandrogenism in adolescent girls is accompanied by augmented LH pulsatility and elevated LH/FSH ratio with increased ovarian volume. Together with higher concentrations of 17-hydroxyprogesterone, androstenedione, testosterone, and estrone that are ovarian in origin, these neuroendocrine features are identical to those seen in adult women with polycystic ovary syndrome. In the present study, we report the metabolic characteristics of these hyperandrogenic adolescent girls. The GH insulin-like growth factor I (IGF-I)-binding protein (BP)-3 axis, insulin sensitivity, and insulin-IGFBP-1/insulin sex hormone binding globulin axes were evaluated in 13 adolescent girls (ages 11-18 yr) with mild to moderate signs of hyperandrogenism (HA) and 28 age-matched normal girls. Insulin sensitivity was assessed by a frequent-sample iv glucose tolerance test (ivGTT, 0.3 g/kg). Twenty-four hour blood samples were obtained at 10-min intervals and were used to determine GH pulsatility (20-min samples), IGFBP-3 levels (0800-0900 h), and fluctuations of insulin, IGFBP-1, and IGF-I (hourly samples) during feeding and fasting phases of the day. In addition, GH responses to GHRH stimulation (1 microgram/kg) were assessed. Fasting insulin concentrations, but not plasma glucose levels, were significantly elevated in the HA group compared with those in the normal group (256 +/- 35 vs. 103 +/- 24 pmol/L, P = 0.0008), as were insulin responses to ivGTT and meals (P < 0.01) and 24-h mean insulin concentrations (P < 0.01). Thus, hyperinsulinemia with normal fasting glucose levels in HA girls may reflect insulin resistance, as suggested by the increased ratio of insulin and glucose (P < 0.001). All measures of insulin were correlated with body mass index (BMI); however, insulin remained significantly higher in the HA group after correcting for BMI, suggesting that decreased insulin sensitivity was related to other factors in addition to BMI. Twenty-four hour IGFBP-1 concentrations showed a diurnal pattern with an inverse relationship to insulin, and 24-h mean concentrations were lower in the HA group (0.35 +/- 0.13 vs. 0.76 +/- 0.09 micrograms/L, P = 0.02). Reduced sex hormone binding globulin levels were also inversely related to insulin levels (P = 0.0007). In contrast, GH pulsatile characteristics and IGF-I/IGFBP-3 levels, as well as GH responses to GHRH, were similar between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1994

Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome.

A study was initiated to delineate the neuroendocrine characteristics of hyperandrogenic adolescent girls with the aim of discerning features that may relate to the pubertal onset of the polycystic ovarian syndrome. Thirteen 11- to 18-yr-old girls with mild to moderate signs of hyperandrogenism (HA) and increased ovarian volume and 28 age-matched normal girls were recruited for the study. LH pulsatility and FSH levels were analyzed based on serum concentrations measured with sensitive immunofluorometric assays in samples taken at 10-min intervals for 24 h under basal conditions, GnRH antagonist (Nal-Glu) suppression, and dexamethasone suppression. Adrenal and ovarian contributions to serum cortisol, dehydroepiandrosterone, androstenedione, testosterone (T), estrone (E1), estradiol (hourly), 17-hydroxypregnenolone, and 17-hydroxyprogesterone (17PO) concentrations were compared during basal and suppression conditions and after gonadotropin and adrenal stimulations by bolus GnRH (10 micrograms) and CRF (1 microgram/kg). The progression from sleep-augmented pulsatile LH secretion to higher LH levels during wake than sleep observed during normal pubertal development occurred 2 yr earlier in the HA group. The number of LH pulses was significantly higher in the HA group during both sleep and waking, whereas pulse amplitude was higher only during the awake time. Thus, mean LH was 2.0-fold higher during the awake time and only 1.6-fold higher during sleep in the HA group compared to the normal group. The elevation of FSH in HA was small relative to that of LH, resulting in an increased LH/FSH ratio (P < 0.008). The HA group had higher concentrations of 17PO (1.8-fold), androstenedione (1.9-fold), T (2.4-fold), and E1 (1.7-fold) than the normal group (all P < 0.001), with no alteration in circadian rhythm. These elevated steroid levels were significantly correlated with LH levels in the basal state and decreased in proportion to the change in LH during Nal-Glu suppression. During adrenal suppression with dexamethasone, concentrations of cortisol, dehydroepiandrosterone, and 17-hydroxypregnenolone decreased in both groups (P < 0.001), but significant suppression of 17PO, T, and E1 occurred only in the normal girls, indicating the ovarian origin of the increased levels of these steroids with enhanced expression of 17 alpha-hydroxylase activity in HA girls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Gonadotrophin releasing hormone pulse generator activity before and during sexual maturation in girls: new insights.

The activity of the gonadotrophin releasing hormone (GnRH) pulse generator during pubertal transition was investigated in 40 healthy girls 7-18 years of age. Ten were pre-pubertal, seven were in early puberty, and 23 were post-menarcheal. Serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured with immunofluorimetric assays, which have a sensitivity approximately 100-fold that of radioimmunoassay, in samples taken at 10-min intervals for 24 h during basal conditions, during Nal-Glu antagonist suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of androstenedione, testosterone and oestradiol were measured by radioimmunoassay. Our data show that the GnRH pulse generator is functionally active in prepubertal girls with selective expression of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a greater increase in LH pulse amplitude than frequency. These overall changes are punctuated by a switch of wake/sleep activities of GnRH pulse generator with a progressive increase in day-time pulsatility and a gradual reduction of sleep-entrained amplification. While LH pulsatility appears to be highly GnRH dependent at all ages, a remarkable decrease in the predominance of GnRH regulation of FSH pulsatility occurs in conjunction with ovarian activation.

Adolescent↗
PubMed1993

Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins.

To delineate the activity of the GnRH pulse generator during pubertal transition, 40 healthy girls 7-18 yr of age were studied. Ten were prepubertal (PP), 7 were in early puberty (EP), and 23 were in late puberty (LP, all postmenarcheal). Serum concentrations of LH and FSH were measured with immunofluorometric assays, which have a sensitivity about 100-fold that of RIA, in samples taken at 10-min intervals for 24 h during basal conditions, during Nal-Glu antagonist suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of androstenedione, testosterone, and estradiol were measured with RIA. A pulsatile pattern of LH and FSH secretion was found in girls of all ages. PP girls had irregular LH pulses with low amplitudes during the daytime, but increased amplitude LH and FSH pulses were evident within 1 h after sleep-onset. Older PP girls had more regular and higher amplitude pulses throughout sleep than younger PP girls. The sleep-related LH and FSH pulses in PP girls were abolished with Nal-Glu GnRH antagonist treatment, reflecting endogenous GnRH pulse activities. The PP group had the most pronounced amplification of LH secretion with sleep yielding a sleep-wake ratio of 4, which decreased to 2 in the EP group and to 1 in the LP group. The emergence of regular daytime LH pulses along with a further amplification of pulsatile activity during sleep was closely related to the onset of breast development. By the age of 16 yr, an LH secretory pattern characteristic of adult women in the early follicular phase, i.e. a decrease in LH concentration during sleep, was established. Mean 24-h LH concentrations increased 40-fold from PP to LP consequent to a 9-fold increase in pulse amplitude and a 4-fold increase in pulse number (both P < 0.0001). Mean FSH concentrations (24 h), which were 20-fold higher than corresponding LH concentrations in the PP group, increased only 3-fold from the PP to the LP group. FSH pulse secretion appears to be predominantly GnRH dependent in PP girls in contrast to girls after ovarian activation, as indicated by the increased FSH responses to both GnRH antagonist suppression and GnRH stimulation in the PP as compared to the EP and LP groups. We conclude that the GnRH pulse generator is functionally active in prepubertal girls with selective expression of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a greater increase in LH pulse amplitude than frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Melatonin rhythms in women with anorexia nervosa and bulimia nervosa.

To discern whether the multiple neuroendocrine-metabolic dysfunctions observed in women with anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered diurnal variations in serum melatonin profiles, we compared cycling and amenorrheic women with normal weight BN (n = 8) and AN (n = 7) to 21 normal cycling controls. Endogenous depression, which has confounded prior studies of melatonin profiles in women with eating disorders, was excluded in all subjects. Serum samples for melatonin measurements were obtained at frequent intervals (every 20 min) in a controlled light-dark environment, and cycling women were studied in the early follicular phase of the menstrual cycle. Mean (+/- SE) peak melatonin levels were similar in AN, BN, and controls (325 +/- 43, 310 +/- 33, and 334 +/- 30 pmol/L, respectively). The time of melatonin peak, the time of onset and offset of the nocturnal serum melatonin excursion, and the duration of the nocturnal elevation were also similar in the three groups. Analysis of covariance revealed no independent effects of age or time of year on the data. Moreover, when subjects were separated into those with and without menstrual cyclicity, no significant differences in any parameter of melatonin diurnal variation were observed. Taken together, these data suggest that pineal melatonin secretion is unaltered in women with eating disorders, in whom depression is excluded, and that the frequent occurrence of amenorrhea in this population is not mediated by melatonin.

Adult↗
PubMed1992

Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes.

The impact of chronic high volume athletic training on thyroid hormone economy has not been defined. We investigated the status of the hypothalamic-pituitary-thyroid axis (H-P-T) in women athletes with regular menstrual cycles (CA) and with amenorrhea (AA). Their data were compared with each other and with those derived from cyclic sedentary women (CS) matched for a variety of confounding factors including the intensity of exercise, caloric intake, and body weight. Alterations of the H-P-T axis were observed in women athletes compared to CS. While serum levels of T4, T3, free T4, free T3 and rT3 were substantially reduced (P less than 0.01) in AA, only serum T4 levels were significantly decreased in CA. Further, remarkable differences were found between CA and AA in that serum levels of free T4 (P less than 0.01), free T3 (P less than 0.01), and rT3 (P less than 0.05) were significantly lower in AA than in CA. Thyroid binding globulin and sex-hormone binding globulin concentrations were within their normal ranges for all groups of subjects. Both 24-h mean TSH levels and the circadian rhythm of TSH secretion were also comparable. However, the TSH response to TRH stimulation was blunted (P less than 0.01) in AA when compared to CA, but not to CS. Whereas the underlying mechanism(s) to account for the "global" reduction of circulating thyroid hormone in the face of normal TSH levels in AA is presently unknown, these observations provide information of clinical significance: 1) chronic high volume athletic training in women athletes with menstrual cyclicity is accompanied by an isolated T4 reduction; 2) an impaired H-P-T axis occurs selectively in athletic women in whom chronic high volume athletic training is associated with compromised hypothalamic-pituitary-ovarian function and amenorrhea.

Adult↗
PubMed1992

A circadian rhythm of serum follicle-stimulating hormone in women.

While a nocturnal decline in serum LH levels in the early follicular phase of the menstrual cycle has been well established, a diurnal variation in serum FSH levels in women has not been demonstrated. We addressed this issue by determining serum LH and FSH levels at 15-min intervals for 24 h in the early follicular phase (EFP; n = 16) and late follicular phase (LFP; n = 10) of the menstrual cycle and in postmenopausal women (PMW; n = 10). Serum estradiol was simultaneously measured at hourly intervals. As expected, EFP, but not LFP and PMW, women had a 15% nocturnal decline (P less than 0.01) in transverse mean LH levels compared to values in the daytime hours. In contrast, nocturnal FSH transverse mean values were significantly lower than daytime values in all groups studied, demonstrating an 18% decline in EFP (P less than 0.001), a 17% decline in LFP (P less than 0.00001), and a 4.3% decline in PMW (P less than 0.01). Cosinor analysis revealed a circadian rhythm for FSH, with acrophases in the afternoon and nadirs at night in all three groups. The circadian amplitudes were 1.43 +/- 0.22, 1.02 +/- 0.16, and 8.42 +/- 1.31 IU/L for EFP, LFP, and PMW, respectively. The EFP nocturnal decline in LH did not conform to a cosine rhythm. A diurnal variation in estradiol was not present in any of the groups of women. These data constitute the first demonstration of a robust circadian rhythm of serum FSH in women. The comparable timing of the acrophase in all groups of subjects and its presence in the postmenopausal years suggest a central, rather than peripheral, feedback mechanism(s) for the circadian rhythmicity. This observation provides strong evidence for a dissociation in the hypothalamic regulation of pituitary LH and FSH secretion in women. The circadian peak and nadir of circulating FSH may prove to be determining for appropriate follicular development.

Adult↗
PubMed1991

Acceleration of luteinizing hormone pulse frequency in functional hypothalamic amenorrhea by dopaminergic blockade.

A constellation of neuroendocrine secretory aberrations, including reduced LH pulse frequency and PRL concentrations, has been documented in women with functional hypothalamic amenorrhea (FHA). As pituitary function was preserved, these aberrations were attributed to an alteration in hypothalamic neuromodulation. To investigate the participation of the dopaminergic system in the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA, we studied six women with FHA and six cyclic women in the early follicular phase by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h infusions of saline and a dopamine receptor blocker, metoclopramide (MCP). A hypothalamic vs. pituitary site of action was inferred from the pulsatility characteristics. MCP consistently elicited an increase in the LH pulse frequency in the women with FHA [7.3 +/- 1.2 (+/- SE) to 10.5 +/- 1.3 pulses/24 h; P less than 0.005]. In contrast, the eumenorrheic women did not show a significant change in LH pulse frequency in response to MCP (15.2 +/- 1.0 to 14.3 +/- 0.9 pulses/24 h). While the PRL concentrations were significantly lower in the FHA group during the infusion of saline (P less than 0.001) and MCP (P less than 0.005), the relative increases in PRL during MCP were similar in both groups. The acceleration of LH pulse frequency by blockade of dopamine receptors implies that there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency in women with FHA.

Adult↗
PubMed1991

Marked augmentation of nocturnal melatonin secretion in amenorrheic athletes, but not in cycling athletes: unaltered by opioidergic or dopaminergic blockade.

Exercise of sufficient intensity during daylight hours has been demonstrated to result in an acute elevation of circulating melatonin levels. The possibility that repeated elevations of daytime melatonin secretion may result in alterations of the nocturnal maxima of the circadian rhythm in highly trained athletic women with and without amenorrhea was investigated. Twenty-four-hour melatonin profiles in matched cyclic sedentary (CS; n = 10) women, cyclic athletic (CA; n = 10) women, and amenorrheic athletic (AA; n = 8) women were compared. The roles of endogenous opioids and dopamine as potential modulators of melatonin secretion were also evaluated by comparing the melatonin profiles during sequential 24-h infusions of saline, followed by either naloxone or metoclopramide (both at 30 micrograms/kg.h). Elevated (P less than 0.05) mean daytime (1000-1700 h) melatonin levels were observed in both groups of athletic women compared to sedentary women. In contrast, nocturnal melatonin levels in sedentary and athletic cycling women were indistinguishable, while amenorrheic athletic women displayed a marked increase in nocturnal peak amplitude (P less than 0.001 vs. CS and CA) and a 2-h delay in offset (P less than 0.001 vs. CS and CA), which yielded a 2-fold amplification of the integrated nocturnal melatonin secretion (P less than 0.001 vs. CS and CA). The onset of the nocturnal rise did not differ among the three groups. Opioidergic and dopaminergic blockade with naloxone and metoclopramide at the doses used did not alter any parameter of melatonin secretion in any of the three groups of women. In conclusion, athleticism in women is associated with an elevation of daytime melatonin levels independent of menstrual status. AA women, but not CA women, display a 2-fold amplification of nocturnal melatonin secretion with a 2-h delay of offset, which does not seem to be linked to athleticism per se. The significance and neuroendocrine basis for the expanded melatonin secretion in athletic amenorrheic women remains to be elucidated.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1990

Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression.

The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome.

Adult↗
PubMed1990

Relative changes in LH pulsatility during the menstrual cycle: using data from hypogonadal women as a reference point.

The basic premise of this study is that the GnRH-LH pulsatile activity, particularly its frequency characteristics, constitutes, in the absence of any considerable ovarian feedback, the intrinsic rhythm of the hypothalamic-pituitary unit at its maximal rate. Thus, LH pulse attributes determined in postpubertal hypogonadal subjects may be used as a reference in assessing the degree of influence exerted by endocrine factors that modulate GnRH-LH pulses. Accordingly, serum LH levels were determined in samples obtained at 15-min intervals for 24 h in 20 hypogonadal women: 13 postmenopausal women (PMW) and seven women with premature ovarian failure (POF). Similar measurements were performed in 60 normally cycling women: 25 in the early follicular phase (EFP), 13 in the late follicular phase (LFP), seven at midcycle surge (LH surge) and 15 in the midluteal phase (MLP). Significant pulses were identified by the cluster algorithm utilizing factors appropriate for 24 h data series of a sampling frequency of 15-min intervals. The results show a 24-h mean (+/- SE) LH pulse frequency of 78.2 +/- 2.8 and 85.5 +/- 2.4 min per pulse for young (POF) and older (PMW) hypogonadal women, respectively. During the follicular phase of the cycle, the LH pulse frequency is not significantly different from that of hypogonadal women, but there is a significant (P less than 0.05) increase from early to late follicular phases (95.4 +/- 3.3 vs 78.8 +/- 2.2 min per pulse). However, when the sleep periods are excluded from the 24-h data series because of the associated decrease of LH pulse frequency in EFP women, the resulting pulse frequencies are almost identical for EFP, LFP and PMW. An elevation beyond the basic pulse rhythm determined in PMW or POF is not observed in any phase of the menstrual cycle studied, including the midcycle surge. The decrease in LH pulse frequency during the luteal phase of the cycle (151.8 +/- 8.0 min per pulse, P less than 0.001 vs hypogonadal women) beyond the reference pulse frequency of hypogonadal women is unequivocal. By contrast, the pulse amplitude varies markedly among the groups with the largest found in POF (36.6 +/- 4.5 IU/l). It follows, in descending order, PMW (22.7 +/- 3.1 IU/l), midcycle surge (17.3 +/- 2.8 IU/l), MLP women (7.0 +/- 1.3 IU/l) and the EFP (4.9 +/- 0.3 IU/l) and LFP (4.0 +/- 0.4 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Secretory dynamics of oestradiol (E2) and progesterone (P4) during periods of relative pituitary LH quiescence in the midluteal phase of the menstrual cycle.

Although the temporal relationship between pulsatile pituitary luteinizing hormone (LH) secretion and steroid hormone release from the corpus luteum has been investigated, the secretory profiles of oestradiol (E2) and progesterone (P4) during periods without any discernible LH pulsatile activity remain unknown. Consequently, blood was sampled at 15-min intervals for 24 h from 16 women during the midluteal phases (6-8 days after midcycle LH surge) of their cycles. LH was measured in all samples and analysed for significant pulses by the Cluster pulse algorithm. Nine studies showing the lowest LH pulse frequencies and large LH pulse amplitudes were also assessed for E2 and P4 in all samples. All three hormones were released in pulsatile fashions. Pulses of E2 and P4 were found to be synchronous. While the release frequencies for E2 (mean +/- SEM: 8.9 +/- 0.7 pulses/24 h) and P4 (8.5 +/- 0.7 pulses/24 h) were comparable, the LH pulse frequency (4.6 +/- 0.4 pulses/24 h) was found to be significantly (P less than 0.001) lower than the ovarian steroid pulse frequencies. Maximum (P less than 0.01) cross-correlation coefficients were determined at positive time lags of 28.1 +/- 7.7 min for LH/E2 and 31.7 +/- 5.8 min for LH/P4, indicating that changes in E2 or P4 levels tended to occur within approximately 30 min following LH concentration changes. Further, the degree of concomitance between a steroid pulse and an LH peak was much higher (P less than 0.001) than by chance. Maximum (P less than 0.01) cross-correlation coefficients between E2 and P4 hormonal data series were found at zero time lag, suggesting that these sex steroids were secreted simultaneously. The pulse amplitudes, pulse durations and areas under the peaks of those E2 or P4 pulses preceded by large (greater than 5 IU/l) amplitude LH pulse were significantly greater (P less than 0.05 or less for all comparisons) than for steroid pulses not associated with preceding LH pulses. Thus, two populations of steroid pulses were observed; one associated with preceding LH pulses and having greater magnitude of all pulse attributes (duration, amplitude, area under the peaks), and another, not associated with preceding LH pulses and having pulse characteristics of lower magnitude. This observation suggests that the pulsatile release of ovarian steroids is a result of the episodic modulating influence of LH and that pulsatile steroid hormone secretion pertains with smaller magnitude during periods of relative pituitary quiescence of LH pulsatility.

Adult↗
PubMed1990

Pulsatile cosecretion of estradiol and progesterone by the midluteal phase corpus luteum: temporal link to luteinizing hormone pulses.

Using recently defined analytical tools that permit quantitative and integrated assessments of pulsatile activities of two or more hormones, we have examined the coincidence of pulses of estradiol (E2), progesterone (P4), and LH determined in blood withdrawn at 15-min sampling intervals for a duration of 24 h in each of 15 women during the midluteal phase of the human menstrual cycle. The occurrence of E2 and P4 pulses is simultaneous, as their peaks were maximally correlated at zero time lag (P less than 10(-4], and there were comparable periodicities for E2 (13.5 +/- 0.7 pulses/24 h) and P4 (11.2 +/- 0.7 pulses/24 h). This coupling of E2 and P4 pulses suggests cosecretion by the mature corpus luteum. These E2 and P4 pulses are significantly coupled with LH pulses, with a lag time of about 30 min and/or 45 min for P4 (P = 0.029) and 0 min and/or 15 min for E2 (P = 0.032). Further, when considered together, LH, E2, and P4 are found to be triply copulsatile (P = 0.0066). However, significant numbers of discrete pulses of P4 and E2 are observed without antecedent LH pulses, suggesting some degree of corpus luteum autonomy. In conclusion, orchestrated synchrony of pulsatile pituitary and ovarian (corpus luteum) signaling can be demonstrated by the coordinated temporal release of LH, E2, and P4 in normal cycling women.

Adult↗
PubMed1990

Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: evidence for a reduced 17,20-desmolase enzymatic activity.

Circulating levels of adrenal delta 5-androgens [dehydroepiandrosterone (DHEA), and its sulfate (DS)] selectively decrease with age in both sexes, while cortisol secretion remains unchanged. The mechanism(s) to account for this dissociation is unclear. We tested the hypothesis that a reduced enzymatic activity for delta 5-androgen biosynthesis may be responsible for this phenomenon by examining the ultradian and circadian rhythmicity (15-min sampling frequency for 24 h) of DHEA and cortisol and the responsiveness of DHEA, DS, and cortisol to human CRF stimulation and by the analysis of relative enzymatic activities in the biosynthesis of adrenal steroids in older postmenopausal women (PMW) and younger cycling women (NCW). Our data show that the timing of the circadian rhythm of DHEA secretion was not altered, but the acrophase amplitude was decreased (P less than 0.01) in aged PMW compared to NCW. While the pulse frequency of DHEA remained unchanged, the pulse amplitude was markedly attenuated in PMW compared with NCW (3.5 +/- 0.6 vs. 8.1 +/- 1.1 nmol/L; P less than 0.01). Correspondingly, the 24-h mean of DHEA was markedly reduced (P less than 0.001) in PMW (5.5 +/- 0.8 nmol/L) from that in NCW (12.1 +/- 1.4 nmol/L). For cortisol, all parameters were similar between the two groups. Thus, compared to NCW, the decline of circulating DHEA level in PMW was expressed by attenuations of pulse amplitude and circadian amplitude, without changes in the timing of the circadian rhythm or pulse frequency. Further, DHEA and DS, but not cortisol, responses to 8-h hCRF infusion were significantly (P less than 0.01) diminished in PMW. These findings together with decreased product/precursor ratios for DHEA/17-hydroxypregnenolone (P less than 0.01) and androstenedione/17-hydroxyprogesterone (P less than 0.05) suggest a reduction of 17,20-desmolase enzymatic activity in PMW compared to that in NCW. Steroid ratios for 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase were unaltered. We conclude from these preliminary data that the disparity of DHEA and cortisol secretion in aged PMW is probably related to an intraadrenal event, resulting from a decrease in 17,20-desmolase expression, which governs the biosynthesis of delta 5-adrenal androgen.

Adrenal Glands↗
PubMed1988

Hypercortisolism in patients with functional hypothalamic-amenorrhea.

Hypercortisolism was found in patients with functional hypothalamic amenorrhea (HA) in preliminary short term studies conducted during the morning hours (0800-1100 h). This observation prompted us to characterize the circadian and pulsatile patterns of serum cortisol and LH levels at 15-min intervals for 24 h in 10 women with functional HA and in 7 normal women during the early follicular phase of their cycles. The mean integrated 24-h serum cortisol levels (area under the curve) were significantly (P less than 0.01) higher in the HA patients than in normal women. The mean cortisol levels in the HA patients were elevated (P less than 0.005) compared to those in the normal women during the daytime hours (0800-1600 h), but not during the evening (1600-2400 h) and sleeping hours (2400-0800 h). This selective hypercortisolism during the waking period of the day was almost entirely related to increased duration and amplitude of secretory episodes (peak area) rather than a change in pulse frequency. The serum cortisol increments in response to a noon meal that occurred in normal women were markedly impaired (P less than 0.01) in the HA patients. Compared with that in the normal women, mean LH pulse frequency was reduced by 30% in the HA patients. The 24-h mean LH levels and mean LH pulse amplitude were not significantly different from those in the normal women. However, among the HA patients there were marked individual differences in LH pulse frequency and amplitude, with prolonged interpulse quiescent periods, indicative of dysfunction of the hypothalamic GnRH pulse generator. We conclude that neuroendocrine activation of the ACTH-adrenal axis and inhibition of the GnRH pulse generator in women are associated with HA. Further, spontaneous resumption of normal cyclicity occurred in the majority (8 of 10) of the HA patients with no medical treatment, suggesting that this syndrome is a reversible hypothalamic disorder of a functional nature.

Adrenocortical Hyperfunction↗
PubMed1988

Dopaminergic control of circadian and pulsatile pituitary thyrotropin release in women.

Dopamine (DA) inhibits pituitary TSH release, but its role as a regulator of circadian and pulsatile TSH secretion is not clear. Accordingly, we studied the 24-h TSH secretory patterns in seven normal women in the early follicular phase of their cycles before and during DA receptor blockade by metoclopramide (MCP). Serum TSH was measured by a highly sensitive (0.05 mU/L) RIA at 15-min intervals for 48 h during sequential 24-h saline and 24-h MCP infusions (30 micrograms/kg.h). Sleep was confirmed by electroencephalogram between 2300-0700 h. All women had a nocturnal rise of TSH, independent of sleep, which began in the late afternoon and reached a peak (acrophase) after midnight during the saline infusion. This circadian periodicity was composed of a series of TSH pulses with greater magnitude and frequency during nocturnal hours. Infusion of MCP had no effect on pulse frequency, but the pulse amplitude increased (P less than 0.05), especially at night. As a consequence, the circadian excursion of TSH, as assessed by cosinor function, was exaggerated. The mean acrophase amplitude and mesor levels increased (P less than 0.05), but the nadir and acrophase times did not change. These findings suggest that DA is an inhibitor of TSH pulse amplitude throughout the 24-h biological clock. By inference, the neuroendocrine mechanism(s) that underlies the nocturnal increase in TSH secretion is not due to decreased dopaminergic inhibition.

Adult↗