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Biomedical subjects

H G Burger

Publications and source records attributed to H G Burger.

At least 127 records · Page 7Linked to original sources
PubMed1989

GnRH agonist administration in polycystic ovary syndrome.

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 micrograms, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P less than 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P less than 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P less than 0.01). There was failure to respond to an intravenous bolus of 100 micrograms of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P less than 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (greater than 3 follicles greater than 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1989

Inhibitory effect of pure 31-kilodalton bovine inhibin on gonadotropin-releasing hormone (GnRH)-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells.

Primary cultures of enzymatically dispersed rat anterior pituitary cells were used to examine the effect of pure 31 kilodalton bovine inhibin on GnRH-induced up-regulation of GnRH binding sites. After 2 days in culture, the cells were exposed to stimuli with or without test substances for 10 h, followed by evaluation of GnRH binding sites using iodinated GnRH-A (Buserelin) as tracer. Inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in a dose-dependent manner with an IC50 of 0.13 U/ml (5.5 pM). The inhibin-related peptides transforming growth factor-beta, and Müllerian inhibitory substance had no detectable effect (stimulatory or inhibitory), suggesting that the action is specific to inhibin. In addition, inhibin inhibited the calcium ionophore A23187-induced up-regulation of GnRH binding sites, indicating that this effect of inhibin can occur, at least in part, at a stage subsequent to Ca2+ mobilization. Inhibin did not compete with iodinated GnRH-A for GnRH binding sites. In conclusion, pure 31 kilodalton bovine inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells, providing direct evidence that inhibin modulates delayed actions of GnRH.

Animals↗
PubMed1989

The importance of luteinizing hormone in the control of inhibin and progesterone secretion by the human corpus luteum.

Serum inhibin levels rise markedly during the luteal phase of the human menstrual cycle and are closely correlated with serum progesterone (P) levels, suggesting that the corpus luteum (CL) secretes inhibin. While FSH is the major regulator of inhibin secretion by the granulosa cells, the control of CL inhibin secretion is unclear. We hypothesized that, like P, CL inhibin secretion would be LH dependent. To examine this possibility, normal women were given the GnRH antagonist [Ac-D2Nal1, D4CL Phe2, D3Pal3, Arg5, DGlu6 (AA), DAla10]GnRH (Nal-Glu antagonist) for 3 consecutive days commencing on day 6-8 of the luteal phase. The daily doses were 2.5 (n = 3), 10 (n = 4), and 25 micrograms/kg (n = 5), sc. Serum LH levels fell 2 h after injection, and the fall was maximal (70-74%) at 6 h; the degree of suppression was not dose dependent. The duration of suppression was dose related, being less than 12 h, between 12, and 24 h, and more than 24 h for the 2.5, 10, and 25 micrograms/kg doses, respectively. Serum FSH levels declined by 22-43%, but the effect was not dose related. Serum P levels fell by 42-45% 8 h after each dose of antagonist. They returned to baseline 24 h after the 2.5 micrograms/kg dose, but after both the 10 and 25 micrograms/kg doses serum P levels continued to fall, and menstrual bleeding commenced within 48-72 h after the first antagonist injection. Serum inhibin levels were not altered relative to normal cycles by the 2.5 micrograms/kg dose, but fell by 48% and 58%, and 62% and 73% respectively, 48 and 72 h after the 10 and 25 micrograms/kg doses, respectively. Serum P and inhibin levels correlated closely in all women. To examine the relative roles of FSH and LH in the control of CL function, Nal-Glu antagonist (25 micrograms/kg, sc) was administered at 0 and 24 h commencing on day 6-8 of the luteal phase, in combination with either human menopausal gonadotropin (hMG; 150 IU, im, every 12 h) or hCG (1500 IU, im, once), both commencing at 0 h. hMG administration led to a rapid (by 2 h) and marked (3- to 9-fold) rise in serum FSH levels, whereas serum LH remained low, similar to antagonist alone treatment cycless.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

A comparison of the suppressive effects of testosterone and a potent new gonadotropin-releasing hormone antagonist on gonadotropin and inhibin levels in normal men.

GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Na1-Glu [AcD2NaL1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 micrograms/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Na1-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1-2 days of Na1-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Na1-Glu administration. The combination of Na1-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Na1-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Na1-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.

Adult↗
PubMed1989

Dynamic changes in circulating inhibin levels during the luteal-follicular transition of the human menstrual cycle.

Dynamic changes in serum immunoreactive (ir) inhibin levels during the transition from the luteal to the follicular phase (luteal-follicular transition) were characterized during 3 consecutive cycles in 12 cycling women. Both spontaneous (first to second cycle) and GnRH antagonist-imposed premature luteolysis (second to third cycle) were evaluated. Serum FSH, LH, estradiol (E2), and progesterone (P4) levels were monitored daily by RIA for the entire study. Daily ir-inhibit levels were determined from 7 days before until 7 days after the onset of menses and from 4 days before to 10 days after the GnRH antagonist-induced bleeding by a heterologous RIA. During spontaneous luteolysis, ir-inhibin levels peaked 7 days before menses and declined in a linear fashion (r = -0.99) thereafter, reaching a sustained low level 1 day after the onset of menses. The decline of P4 and E2 levels appears to be coupled to that of ir-inhibin (r = 0.98 and r = 0.95, respectively). FSH levels showed an inverse pattern, with an acute elevation unaccompanied by LH, for 5 days before the onset of menses and reaching a plateau 2 days after. ir-Inhibin and FSH were negatively correlated (r = -0.87; P less than 0.0001). Increased LH levels did not occur until the day of menses and were negatively correlated with ir-inhibin (r = -0.50; P less than 0.05), but not E2 and P4. During the second cycle, at the midluteal phase luteolysis was induced by a single (50 micrograms/kg) im injection of a potent GnRH antagonist, [Ac-D2Nal,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10] GnRH; an acute decline of LH and FSH levels occurred, with maximal suppressions of 51% and 35%, respectively. ir-Inhibin levels decreased rapidly (40 +/- 2.8%) in parallel with E2 and P4 during the first 24 h and continued to decline for 4 days. The inverse relationship and time course of changes between FSH and ir-inhibin levels were similar to those of the spontaneous luteal-follicular transition. Six of the 12 subjects experienced partial reversal of luteolysis; the decline of ir-inhibin and the rise of FSH during the first 2 days were arrested for 4 days, which corresponded to the rebound increases in E2, P4, and LH. The subsequent fall of ir-inhibin was followed by a rise in FSH. Both the complete and incomplete luteolysis groups exhibited an orderly follicular maturation, LH surge, and luteal function during the ensuing cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Serum inhibin levels in normal men and men with testicular disorders.

Serum concentrations of inhibin, FSH and LH were measured in 39 normal men and 127 men with testicular disorders resulting in infertility. The infertile men were divided into groups on the basis of their mean sperm count, FSH levels and karyotype. The mean (+/- S.D) serum concentrations of inhibin in the normal men was 554 +/- 156 U/l and did not differ significantly from those groups with oligospermia, azoospermia or Klinefelter's syndrome. Combined analyses of all groups did not reveal any significant correlation between serum concentrations of inhibin and FSH or with any other parameter measured. Serum concentrations of FSH and LH were positively correlated, and Leydig cell dysfunction, as evidenced by increased serum LH levels, low testosterone levels or a declining testosterone/LH ratio were found with severe spermatogenic damage. The failure of serum concentrations of inhibin to correlate with those of FSH levels or the degree of testicular damage raise questions as to the clinical value of this parameter alone.

Adult↗
PubMed1989

Purified FSH stimulates production of inhibin by the human ovary.

Ovarian inhibin production is stimulated by the administration of human menopausal gonadotrophins or following a rise in endogenous LH and FSH. In order to determine whether FSH specifically stimulates inhibin secretion in vivo, immunoassayable serum inhibin levels were measured following the administration of a highly purified preparation of urinary FSH free of significant contamination with LH. Ten anovulatory women underwent a protocol of induction of ovulation with purified FSH and human chorionic gonadotrophin (hCG). During the induction of ovulation, blood samples were taken for radioimmunoassay of FSH, LH, oestradiol, progesterone and inhibin. During the administration of FSH there were increases in plasma concentrations of FSH, oestradiol and inhibin (P less than 0.01) but no significant change in the concentration of LH. Oestradiol and inhibin concentrations rose in parallel and were closely correlated (tau = 0.920, n = 110, P less than 0.001). There was also a direct correlation between the measured level of FSH and inhibin (tau = 0.512, n = 110, P less than 0.05), but there was no correlation between LH and oestradiol, inhibin or FSH. Inhibin (tau- = 0.702, n = 10, P less than 0.01) and oestradiol (tau- = 0.691, n = 10, P less than 0.01) were correlated with the number of follicles seen on ovarian ultrasound. Levels of oestradiol and inhibin reached a peak on the day of hCG administration or on the following day. Inhibin levels then fell over the next 2 days in all cycles. In an ovulatory cycle resulting in conception, inhibin and oestradiol then rose in parallel with progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1988

Selective control of rat granulosa cell inhibin production by FSH and LH in vitro.

We studied the role of luteinising hormone (LH) and human chorionic gonadotropin (hCG) in regulation of rat granulosa cell inhibin production. Whereas pregnant mare serum gonadotropin (PMSG) or purified rat follicle-stimulating hormone (FSH) stimulated inhibin accumulation in culture media up to 6-fold in a dose-dependent manner, hCG or LH alone were without significant effect. Concomitant addition of hCG or LH to cultures containing half maximal or maximal stimulating concentrations of PMSG did, however, result in a dose-dependent inhibition of PMSG/FSH-induced inhibin production. However, in the 2-step culture system a biphasic effect of hCG treatment on FSH-primed granulosa cell inhibin and progesterone production was evident. hCG was only inhibitory when the cells in the 2-step system were primed with PMSG. These data indicate that granulosa cell inhibin production is under direct control of both FSH and LH, and provide a possible explanation for alterations in inhibin activity around the time of ovulation in vivo.

Animals↗
PubMed1988

Transforming growth factor beta enhances basal and FSH-stimulated inhibin production by rat granulosa cells in vitro.

Transforming growth factor beta (TGF beta) caused a dose-dependent increase in both basal and follicle-stimulating hormone (FSH)-stimulated inhibin production by rat granulosa cells in culture. The TGF beta dose-response curve in the absence of FSH was approximately parallel to that in the presence of either a minimally effective dose (1 ng/ml) or a maximally effective dose (30 ng/ml) of FSH, suggesting an additive effect of these two agents on inhibin production. There was also a suggestion of an increased sensitivity of granulosa cell inhibin production to FSH when the cells were coincubated with TGF beta. The time course study showed that similar to FSH, the stimulatory effect of TGF beta on basal and FSH-stimulated inhibin production was evident on day 1 and was maximal by day 4. In addition, epidermal growth factor (EGF) reduced FSH-stimulated inhibin production with an ID50 value of 1.3 ng/ml. Coincubation of cells with EGF and 1 ng TGF beta/ml enhanced greatly the inhibitory action of EGF on FSH-induced inhibin production (ID50 less than 0.1 ng/ml). It is concluded that: (1) TGF beta directly stimulates inhibin production by rat granulosa cells and the combined effect with FSH was largely additive, (2) the inhibitory effect of EGF on FSH-induced inhibin production was enhanced by TGF beta, (3) individual members of the TGF beta/inhibin gene family regulate ovarian function, not only by direct action on follicle cells but also indirectly by influencing the production rate of other members of that family.

Animals↗
PubMed1988

Plasma inhibin levels in men with chemotherapy-induced severe damage to the seminiferous epithelium.

Immunoreactive plasma inhibin levels and free testosterone index (FTI) were estimated in 17 patients who had previously received combination chemotherapy for Hodgkin's disease and in 16 age-matched controls. In the same patients we had previously found significantly raised FSH and LH levels in the presence of normal basal and HCG-stimulated total testosterone levels. Mean plasma inhibin levels were not different between the patients (601 +/- 321 U/l) and controls (530 +/- 174 U/l) nor were FTI values (81.5 +/- 35 vs 91 +/- 47 respectively). There was a positive correlation (r = 0.53, P less than 0.05) between FSH and inhibin levels and a negative correlation between FSH and FTI (r = -0.51, P less than 0.05) in the patients but not in the controls. No such correlations with inhibin or FTI existed for LH but there was a positive correlation between LH and FSH levels in the patients. In four patients inhibin levels were pathologically raised and in this group mean FSH values (21.7 +/- 4.7 IU/l) were higher (P less than 0.001) and mean FTI (59.1 +/- 22.6) lower (P less than 0.001) than respective values (13.6 +/- 5.3 IU/l and 88.4 +/- 35) for the remainder of the patients. These data are not compatible with the hypothesis that inhibin is the major negative feedback signal for the control of FSH secretion.

Adolescent↗
PubMed1988

Relative roles of follicle-stimulating hormone and luteinizing hormone in the control of inhibin secretion in normal men.

The glycoprotein hormone inhibin is produced by the Sertoli cells of the testis under the influence of follicle-stimulating hormone (FSH) and is postulated in turn to inhibit FSH secretion. Luteinizing hormone (LH) is not recognized to have an important role in the control of inhibin secretion in any species. To determine the relative roles of FSH and LH in the control of inhibin secretion in man, we examined the effects of selective FSH and LH replacement on serum inhibin levels in normal men whose endogenous gonadotropins were suppressed by testosterone (T). After a 3-mo control period, nine men received 200 mg T enanthate i.m. weekly for 3-9 mo. During T treatment, serum LH and FSH levels were markedly suppressed and serum inhibin levels fell to 40% of control values. While continuing T, 3-5 mo of treatment with purified hFSH (n = 4) or hLH (n = 4) increased the respective serum gonadotropin level into the upper normal range and significantly increased inhibin levels back to 64 and 55% of control values, respectively. Supraphysiological LH replacement with high doses of human chorionic gonadotropin (n = 3) returned serum inhibin levels to 63% of control values. In no case did inhibin levels return fully to control levels. In conclusion, serum inhibin levels fell during gonadotropin suppression and were partially and approximately equally restored by either FSH or LH treatment. FSH presumably acts directly on the Sertoli cell to increase inhibin secretion whereas LH may act via increases in intratesticular T levels and/or other factor(s).

Adult↗