Preserved inhibitory effect of recurrent hypoglycaemia on the male gonadotrophic axis

OBJECTIVE: Hypoglycaemia-induced decreases in male LH and testosterone concentrations are possibly mediated by activation of the hypothalamus-pituitary-adrenal (HPA) axis or by an increase in PRL. As counterregulatory stress hormone release is attenuated during recurrent hypoglycaemia, we questioned whether the gonadotrophic axis and PRL adapt similarly. DESIGN: We performed two consecutive hypoglycaemic clamps on day 1 and one clamp on the following day in 15 healthy men. Blood concentrations of gonadotrophins, PRL, testosterone, ACTH and cortisol were measured during the first and the third clamp, taking place at the same time of day. RESULTS: During hypoglycaemia, serum concentrations of LH and testosterone decreased (P < 0.003 for both), PRL, ACTH and cortisol increased (P < 0.001), and FSH remained unchanged (P = 0.90). The hypoglycaemia-induced decreases in LH and testosterone concentrations were similar during the first and the last clamp (P > 0.28 for both) whereas the increase in PRL, ACTH and cortisol was markedly attenuated during the third clamp (P < 0.001). CONCLUSIONS: LH and testosterone responses do not adapt to recurrent hypoglycaemia, whereas the increase in PRL is attenuated, indicating adaptation. Considering the marked decrease in the responses of PRL and the HPA axis after antecedent hypoglycaemia, the data suggest that the hypoglycaemia-induced decreases in LH and testosterone concentrations, not adapting to recurrent hypoglycaemia, are mediated independently, probably by blood glucose itself.     

Cortisol and androgen secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy.

Bilateral paratesticular tumors were observed in a 32-yr-old man 14 yr after he developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome). Plasma ACTH concentrations were markedly elevated (mean, 6350 pg/ml), but urinary free cortisol concentrations were low (27-31 micrograms/24 h). Catheterization revealed a spermatic to peripheral venous gradient for cortisol consistent with secretion of this steroid by the tumor. This was confirmed by decreased cortisol excretion after tumor excision. Serum androgen (testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone-sulfate) and progestin (progesterone and 17-hydroxyprogesterone) concentrations were decreased and did not decline further after tumor removal. These latter observations suggested that the paratesticular tumors did not secrete appreciable testosterone or any of its immediate precursors. Serum gonadotropin levels were also low. Cyproheptadine treatment resulted in a marked lowering of plasma ACTH concentrations (221-320 pg/ml). This was associated with an increase in both plasma LH and testosterone concentrations. These observations are consistent with the hypothesis that ACTH may directly affect LH and testosterone secretion.     

Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats

The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of the secretion of luteinizing hormone due to isolation/restraint stress in gonadectomised rams and ewes is influenced by sex steroids

In this study we used an isolation/restraint stress to test the hypothesis that stress will affect the secretion of LH differently in gonadectomised rams and ewes treated with different combinations of sex steroids. Romney Marsh sheep were gonadectomised two weeks prior to these experiments. In the first experiment male and female sheep were treated with vehicle or different sex steroids for 7 days prior to the application of the isolation/restraint stress. Male sheep received either i.m. oil (control rams) or 6 mg testosterone propionate injections every 12 h. Female sheep were given empty s.c. implants (control ewes), or 2x1 cm s.c. implants containing oestradiol, or an intravaginal controlled internal drug release device containing 0.3 g progesterone, or the combination of oestradiol and progesterone. There were four animals in each group. On the day of application of the isolation/restraint stress, blood samples were collected every 10 min for 16 h for the subsequent measurement of plasma LH and cortisol concentrations. After 8 h the stress was applied for 4 h. Two weeks later, blood samples were collected for a further 16 h from the control rams and ewes, but on this day no stress was imposed. In the second experiment, separate control gonadectomised rams and ewes (n=4/group) were studied for 7 h on 3 consecutive days, when separate treatments were applied. On day 1, the animals received no treatment; on day 2, isolation/restraint stress was applied after 3 h; and on day 3, an i. v. injection of 2 microg/kg ACTH1-24 was given after 3 h. On each day, blood samples were collected every 10 min and the LH response to the i.v. injection of 500 ng GnRH administered after 5 h of sampling was measured. In Experiment 1, the secretion of LH was suppressed during isolation/restraint in all groups but the parameters of LH secretion (LH pulse frequency and amplitude) that were affected varied between groups. In control rams, LH pulse amplitude, and not frequency, was decreased during isolation/restraint whereas in rams treated with testosterone propionate the stressor reduced pulse frequency and not amplitude. In control ewes, isolation/restraint decreased LH pulse frequency but not amplitude. Isolation/restraint reduced both LH pulse frequency and amplitude in ewes treated with oestradiol, LH pulse frequency in ewes treated with progesterone and only LH pulse amplitude in ewes treated with both oestradiol and progesterone. There was no change in LH secretion during the day of no stress. Plasma concentrations of cortisol were higher during isolation/restraint than on the day of no stress. On the day of isolation/restraint maximal concentrations of cortisol were observed during the application of the stressor but there were no differences between groups in the magnitude of this response. In Experiment 2, isolation/restraint reduced the LH response to GnRH in rams but not ewes and ACTH reduced the LH response to GnRH both in rams and ewes. Our results show that the mechanism(s) by which isolation/restraint stress suppresses LH secretion in sheep is influenced by sex steroids. The predominance of particular sex steroids in the circulation may affect the extent to which stress inhibits the secretion of GnRH from the hypothalamus and/or the responsiveness of the pituitary gland to the actions of GnRH. There are also differences between the sexes in the effects of stress on LH secretion that are independent of the sex steroids.     

Activity of the pituitary-adrenocortical system and thyroid gland during the oestrous cycle of the rat.

The concentrations of LH, progesterone, ACTH, corticosterone and thyroxine in the plasma were estimated at various times during the oestrous cycle of the rat. The well-established patterns of LH and progesterone secretion were confirmed. On each day of the cycle the plasma concentrations of ACTH and corticosterone were lowest in the morning and rose in the afternoon. Conversely, during oestrus and dioestrus, the plasma concentrations of thyroxine were higher in the morning than in the evening. However, during the afternoon of pro-oestrus the concentrations of ACTH, corticosterone and thyroxine in the plasma rose and, like the concentrations of LH and progesterone, all reached levels far higher than those attained at any other time of the cycle.     

Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion

In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.     

Hypothalamic-pituitary-testicular system and adrenocortical function.

Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.     

THE EFFECT OF ANDROGEN BLOCKADE ON PULSATILE GONADOTROPHIN RELEASE AND LH RESPONSE TO NALOXONE

In order to clarify the effects of androgen blockade on the hypothalamic-pituitary-testicular axis in man, four patients with advanced prostate cancer, not previously treated, were given oral flutamide, 250 mg three times daily for 9 days. Before, and 7, 8 and 9 days after starting flutamide treatment, on separate days, the following tests were performed: a gonadotrophin pulsatility study, with 20 min interval blood sampling for 12 h, a naloxone test and a GnRH test. Flutamide induced a significant increase in both LH and FSH pulse frequency, while pulse amplitudes and plasma integrated concentrations (IC) of LH and FSH were unaffected. Plasma integrated concentrations of testosterone and oestradiol rose significantly, while that of prolactin was unaffected. The increase in plasma LH concentration induced by naloxone injection was abolished by flutamide treatment. On the other hand, the small FSH response to naloxone was unaffected by flutamide treatment. Response to GnRH was unaffected by flutamide. These results suggest that flutamide exerts effective androgen blockade at the hypothalamic level, since, despite increased plasma testosterone concentrations, gonadotrophin pulse frequency increased and the LH response to naloxone was abolished.     

Gonadotropin, ACTH, prolactin, sexual steroid and cortisol levels in postmenopausal women's cerebrospinal fluid (CSF)

In CSF and serum of 24 fertile (34.9 +/- 12.2 years) and 15 postmenopausal (58.9 +/- 6.9 years) female patients with non-inflammatory neurologic diseases, LH, FSH, ACTH, prolactin (Prol), estradiol (E), progesterone (P), testosterone (T), and cortisol (C) levels were determined by RIA. In postmenopause, serum levels of FSH and LH had 8- and 6-fold increases in comparison to those in reproductive age. In postmenopause, serum levels of E, P, ACTH and Prol had 8-, 5-, 3- and 2-fold decreases. Serum levels of T and C remained statistically unchanged during the whole life span. In postmenopause, CSF levels of FSH and LH had 3- and 2-fold increases, while E, P, Prol, ACTH CSF levels remained statistically unchanged compared to those in reproductive age (CSF-C levels were under the test sensitivities). CSF/serum ratio of FSH had a 4-fold decrease while that of E had a 4-fold increase in the postmenopause. CSF and serum levels of estradiol and ACTH as well as the logarithmic values of FSH, Prol and P concentrations correlated significantly regarding the whole reproductive postmenopausal life span, however, the CSF-blood barrier seemed to protect the brain from the effects of peripheral estradiol-progesterone deficiencies.     

Effect of long-term androgen treatment on the function of hypothalamo-hypophysial and -adrenal axes in transsexual agonadal women

The study was aimed at assessing the influence of prolonged (18-24 months) androgen treatment of 11 agonadal transsexual women on basal concentrations of LH, FSH, testosterone (T), estradiol (E2), progesterone (P) and SHBG, on the hypothalamic-hypophysial (GH, PRL, ACTH) and hypothalamic-adrenal (cortisol) response in insulin test and TSH and PRL response after TRH administration. Fifteen healthy women in follicular phase of menstrual cycle and 15 men served as controls. In TS women basal concentrations of E2 were comparable with those in healthy women in follicular phase and the lowered T value showed negative correlation with SHBG. In most TS women the stimulated secretion of GH, PRL, ACTH and cortisol in insulin test was diminished. Basal values of these hormones oscillated within normal range except ACTH levels which were higher as compared with control values. In most cases the PRL response to TRH was diminished, but in three patients excessive secretion of PRL was found. Long-term priming with androgen was found to produce a dramatic change in the patterns of hormonal response to post-insulin hypoglycaemia and TRH in female-to-male transsexuals. It was concluded that in prolonged treatment of agonadal transsexual women the doses of testosterone preparations should be adjusted to individual patients in order to monitor steroid and gonadotropin hormone values, as well as the response of pituitary hormones, particularly that of PRL, to stimuli.     

Effects of gonadotropins and adenocorticotropin on plasmatic steroids of the catfish, Heteropneustes fossilis (Bloch).

The levels of some steroids in the plasma of female catfish were estimated following a single injection of porcine ACTH, ovine LH, or partially purified salmon gonadotropin (SG-G100) during the spawning and postspawning seasons. In the regressed catfish, injection of either LH or SG-G100 resulted in a three- to fourfold increase, compared to uninjected controls, in plasmatic cortisol for at least 1 hr. Injection of LH and ACTH resulted in two- and fourfold increases, respectively, of plasma cortisol levels as compared to saline-injected controls for both regressed and gravid fish. The concentration of plasma cortisol after ACTH treatment was higher than after LH or SG-G100. Gonadectomy did not influence the effect of LH on plasma cortisol concentration, and 20 min after injection, the cortisol concentration was identical to that of the intact fish. These results show that in the gravid catfish, as in the regressed ones, the increase in plasmatic cortisol after injection of LH or SG-G100 results principally from the activation of the interrenal. The concentrations of 11-deoxycortisol, 11-deoxycorticosterone, and 17α-hydroxy-20β-dihydroprogesterone were low in all samples and there was no evidence of an effect related to the injected hormone. Testosterone concentrations in the plasma of gravid fish injected with LH increased over the 1-hr sampling time and all values were higher than those recorded for saline- or ACTH-injected fish. Since the levels of cortisol and testosterone in the plasma of gravid catfish increase following gonadotropin administration, they may either singly or synergistically play a role in oocyte maturation.     

Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of corticoliberin and naloxone on the functional activity of the hypophyseal-gonadal system in monkeys]

Experiments were staged on male Papio hamadryas for a study of CRF and naloxone action on the time course of LH and testosterone in peripheral blood. LH was determined by a biological micromethod in vitro; ACTH, cortisol and testosterone were determined by radioimmunoassays. Exogenous CRF was shown to increase inhibitory action of acute "procedure" stress (frequent fixation of monkeys and venipuncture for taking blood samples) of the secretion of LH but not testosterone. Opioid preceptor blockade with naloxone prevented the appearance of inhibitory action of stress and CRF on hypophyseal gonadotropic function rather than on testicular secretory activity. The time course of LH and testosterone after naloxone administration of naloxone combined with CRF has shown that inhibition of testosterone secretion in stress does not depend on a response of gonadotropins and is determined by other (additional) factors.     

Effects of adrenocorticotropin and corticosterone on the negative feedback action of testosterone in the adult male rat

Injections of ACTH (Synacthen depot) to intact male rats resulted in high serum levels of corticosterone and progesterone, and decreased levels of LH, FSH, and testosterone. In gonadectomized rats with low serum testosterone levels (approximately 1 ng/ml) induced by a small testosterone-filled silicone elastomer capsule, ACTH inhibited the postcastration rise in LH and FSH and reduced the wts of the prostate and seminal vesicles. After adrenalectomy the inhibitory effects of ACTH on serum gonadotropins and organ wts were almost totally absent. Administration of corticosterone acetate (10 mg/day) to gonadectomized and adrenalectomized male rats resulted in high serum levels of corticosterone (approximately 400 ng/ml) which were about 3 times higher than those measured in intact control animals. Nevertheless, in these rats the serum levels of LH and FSH were as high as those measured in gonadectomized and adrenalectomized oil-treated rats. However, when in addition to the injections of corticosterone acetate, a small testosterone-filled capsule was implanted, the postcastration rise in FSH was fully inhibited, whereas the serum levels of LH were below the level of detection. Significant inhibition of the postcastration rise in LH and FSH also occurred when smaller quantities of corticosterone acetate were given. Since in gonadectomized and adrenalectomized male rats similar testosterone-filled capsules did not prevent the postcastration rise in LH and FSH, it is concluded that a high serum level of corticosterone increases the sensitivity to the negative feedback effects of testosterone.     

新的DAX-1基因突变致先天性肾上腺发育不全一例的临床及表观遗传学研究

分析一例先天性肾上腺发育不全(AHC)患者的激素和表观遗传学特征.该患者血ACTH升高,皮质醇、睾酮、LH和FSH降低,GnRH和人绒毛膜促性腺激素(hCG)刺激后LH、FSH和睾酮水平无明显升高,DAX-1基因第一外显子C368F突变.     

Partial 17, 20-desmolase and 17 alpha-hydroxylase deficiencies in a 16-year-old boy

Thirteen plasma steroids as well as ACTH, LH and FSH were measured by specific RIAs under basal and dynamic conditions in a 16-year-old boy (normal external genitalia, 46, XY karyotype) who presented slowness and unachievement of pubertal development. On the delta 4-pathway: basal levels of testosterone and dihydrotestosterone were low- with a normal ratio-, delta 4-androstenedione and 11 beta-hydroxyandrostenedione were in the low normal range. Meanwhile, 17 alpha-hydroxyprogesterone and progesterone levels were markedly elevated. On the delta 5-pathway: dehydroepiandrosterone was extremely low while 17 alpha-hydroxypregnenolone and pregnenolone were almost normal; dehydroepiandrosterone sulfate was subnormal while pregnenolone sulfate was normal. Cortisol, aldosterone were normal while ACTH was moderately increased. Basal and responsive levels of LH and FSH were markedly increased. ACTH stimulation induced a subnormal rise of cortisol and 11 beta-hydroxyandrostenedione, a low or absent rise of dehydroepiandrosterone, 17 alpha-hydroxypregnenolone, androstenedione and 17 alpha-hydroxyprogesterone contrasting with a marked rise of pregnenolone and progesterone. After hCG stimulation, responses were low for testosterone, extremely high for 17 alpha-hydroxyprogesterone with a normalisation of the 17 alpha-hydroxyprogesterone/progesterone ratio. Fluoxymesterone dramatically reduced the pathologically high basal levels of progesterone and 17 alpha hydroxyprogesterone. Dexamethasone induced only a minute decrease in the delta 4-progestagens, a marked decrease in pregnenolone, with a more than 80% reduction of 17 alpha- hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and androstenedione. These data suggest a defect involving the cytochrome P450 common to both 17 alpha-hydroxylase and 17, 20-desmolase activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of chronic osteoarthritis pain on neuroendocrine function in men

CONTEXT: Chronic pain has been associated with elevated cortisol, reduced LH and testosterone (T), and/or augmented circulating or excreted catecholamines. Most endocrine studies have been conducted in patients in whom the potentially confounding effects of depression, inflammatory disease, or coexistent medication use have not been controlled. OBJECTIVE: The objective of the study was to test the hypothesis that chronic pain activates ACTH-cortisol and suppresses LH-T. DESIGN AND SETTING: This was a case control study conducted at a clinical research center. PARTICIPANTS: Participants included 16 opioid-naive men with chronic osteoarthritis pain, aged 35-65 yr with body mass index 20-30 kg/m2, and 12 healthy, opioid- and pain-free men of similar ages and body mass indexes. METHODS: We compared circulating concentrations of ACTH, cortisol, LH, and T derived from every 20-min blood sampling (2000-0800 h), and 24-h urinary excretion of cortisol, epinephrine, norepinephrine, and dopamine. RESULTS: There were no significant differences in mean or integrated concentrations of ACTH, cortisol, LH, or T, or in the corresponding approximate entropy scores in osteoarthritis patients, compared with control subjects. The 0800-h serum LH concentrations were elevated in patients vs. controls (6.42 +/- 1.65 vs. 3.99 +/- 1.54 IU/liter, mean +/- sd, P = 0.02), whereas there were no significant group differences in total or free T, SHBG, cortisol binding globulin, dehydroepiandrosterone sulfate, or urinary cortisol and catecholamines. CONCLUSIONS: These data suggest that neuroendocrine function is not significantly altered in otherwise healthy men with chronic musculoskeletal pain and that prior reports of such hormonal abnormalities may have resulted from the confounding effects of coexistent illness or medication use.     

Effect of testosterone on gonadotrophin-releasing hormone receptors in the castrated rat: preliminary evidence for a stimulatory effect of testosterone on gonadotrophin function in the male rat

In the long-term castrated rat the negative feedback effect of testosterone is markedly reduced and the raised levels of plasma LH seen in the castrated animals are not suppressed by physiological concentrations of plasma testosterone. In this study we have measured pituitary gonadotrophin-releasing hormone (GnRH) receptor content as well as plasma and pituitary LH on days 1, 10 and 40 after castration and noted the effect of testosterone replacement on these parameters. We found that the negative feedback effect of physiological concentrations of testosterone on plasma and pituitary LH, pituitary GnRH receptor content and response to exogenous GnRH was attenuated 10 and 40 days after castration. It is suggested that the lack of effect of testosterone in the long-term castrated rat is due to its inability to reduce the pituitary GnRH receptor content. On increasing testosterone to supraphysiological levels, the negative feedback effect was reinstated. We also found that in rats 40 days after castration, physiological and subphysiological concentrations of testosterone significantly increased pituitary GnRH receptor content and this may explain the previous findings that low concentrations of testosterone can enhance the effect of GnRH and increase plasma LH levels.     

ADRENAL FUNCTION IN SUBGROUPS OF THE PCO SYNDROME ASSESSED BY A LONG ACTH TEST

Fifteen patients with the polycystic ovarian (PCO) syndrome were classified into Group A (n = 6) and Group B (n = 9) based on their LH responses to LHRH before and at 44 and 92h after administration of oestradiol benzoate. Adrenal function in both groups was assessed by comparing the hormone responses to ACTH (0.5mg twice daily for 4 days) with those obtained in nine normally ovulating women during the early follicular phase of their cycles. In Group A patients there was no significant difference from normals in the serum concentration of dehydroepiandrosterone sulphate (DHAS), 17 alpha-hydroxy-progesterone (17-OHP) or androgens (testosterone and dihydrotestosterone). In contrast, the serum concentrations in Group B were significantly higher (P less than 0.01) for each of these steroids before ACTH, and remained higher at 2 and 4 days for DHAS, but not for the other two steroids. The concentration of oestrone was significantly higher (P less than 0.05) in Group B patients before, and 2 days after, ACTH, while in Group A patients higher concentrations (P less than 0.02) were found only after 2 days. The concentrations of oestradiol, on the other hand, were not different from normal in either group before ACTH and became lower than normal in both groups at 2 days and remained lower at 4 days in Group B. The concentration of cortisol was within the normal range throughout in Group A, but was lower than normal after 4 days in Group B patients (P less than 0.05). The ratios between the sums of concentrations of DHAS to cortisol on days 2 and 4 (P less than 0.001) or 17-OHP to cortisol (P less than 0.05) were elevated in Group B compared with normal subjects. LH, FSH and prolactin values were normal throughout in Group A, but in Group B patients the mean value for LH was significantly elevated before ACTH and at 4 days after ACTH (P less than 0.02).     

A detailed examination of the in vivo and in vitro effects of ACTH on gonadotropin secretion in the adult rat

These studies were designed to: (1) determine the effects of continuous infusion of synthetic ACTH(1-24) on postcastration changes in serum and pituitary LH, FSH and prolactin in the male rat; (2) assess the effects of adrenalectomy on the gonadotropin and prolactin response to ACTH, and (3) test the hypothesis that ACTH may directly (not via adrenal factors) alter gonadotropin secretion at the brain and/or pituitary level. Adult male rats were either orchidectomized (ORX) or orchidectomized-adrenalectomized (ORX-ADX), and were treated continuously for 6 days with ACTH(1-24) (10 micrograms/day) or saline using an osmotic minipump. Animals were killed on day 6 following castration. ACTH treatment reduced serum LH and prolactin levels in ORX rats to mean values +/- SE of 204 +/- 25 and 37 +/- 3 ng/ml respectively, compared to 366 +/- 72 and 62 +/- 7 ng/ml in saline-treated ORX animals. Serum FSH concentrations were not altered by ACTH administration. Pituitary concentrations of LH and FSH, but not prolactin were enhanced by ACTH treatment. Adrenalectomy had no effect on serum and pituitary gonadotropin and prolactin levels, but abolished the effects of ACTH on these parameters. Central (intracerebroventricular) infusion of ACTH(1-24) (6 micrograms/day X 4 days) failed to alter the rise in serum LH in male rats following orchidectomy. Acute treatment with large doses of ACTH of perifused anterior pituitary glands from male rats and chronic treatment with ACTH of enzymatically dispersed anterior pituitary cells from female rats did not influence basal or GnRH-stimulated LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)