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Biomedical subjects

H G Burger

Publications and source records attributed to H G Burger.

At least 145 records · Page 8Linked to original sources
PubMed1988

Effects of 31 kilodalton bovine inhibin on follicle-stimulating hormone and luteinizing hormone in rat pituitary cells in vitro: actions under basal conditions.

The effects of purified 31 kilodalton (kDa) bovine inhibin on the basal release and cell contents of FSH and LH in pituitary cells from adult male Sprague-Dawley rats have been investigated for periods up to 28 days in tissue culture. A constant rate of basal FSH release (1.90 +/- 0.24 ng/10(6) cells.h) was observed during the first 10 days of culture and this release was blocked by inhibin in a concentration-dependent manner (IC50 = 0.16 U/ml, IC100 greater than 2.5 U/ml). The constant basal LH release between days 2 and 12 of culture (0.15 +/- 0.02 ng/10(6) cells.h) was also blocked by inhibin in a concentration-dependent manner to a minimum of 25% of control (IC50 = 0.66 U/ml, ICmax greater than 6 U/ml). FSH and LH cell contents decreased exponentially in the presence and absence of inhibin over the first 20 days of culture permitting the calculation of decay half-times (t1/2). Inhibin reduced the FSH cell content t1/2 from 5.0 to 1.8 days and the LH cell content t1/2 from 5.8 to 3.6 days (IC50 = 0.81-0.83 U/ml, ICmax greater than 6 U/ml for both FSH and LH). The sum of the FSH released and FSH cell content (i.e. total FSH) increased with time in culture and this increase was blocked by inhibin. In contrast, total LH decreased with time in all cultures. The data suggest that in pituitary cells separated from hypothalamic and gonadal inputs 1) inhibin primarily suppresses tonic FSH synthesis coupled to its basal release; 2) at higher concentrations inhibin partially suppresses basal LH release and promotes intracellular degradation of FSH and LH. Thus, based on differences in sensitivity, inhibin acts at two or more sites, one associated with FSH tonic synthesis-basal release and the other(s) with FSH/LH mobilization and/or degradation.

Animals↗
PubMed1988

Effect of purified 31K bovine inhibin on the specific binding of gonadotropin-releasing hormone to rat anterior pituitary cells in culture.

The mechanism by which inhibin decreases the responsiveness of the pituitary gonadotroph to GnRH in terms of secretion of gonadotropins is largely unknown. We studied the effect of pure 31K bovine inhibin on the specific binding of GnRH to rat anterior pituitary cells in culture using iodinated Buserelin as tracer. Results showed that treatment of cultured anterior pituitary cells from adult male rats with inhibin (0-30 U/ml) for 72 h decreased Buserelin binding in a dose-dependent manner. In the presence of a maximally inhibiting dose of manner. In the presence of a maximally inhibiting dose of inhibin, Buserelin binding decreased progressively with time, reaching a minimum of 42% of the control value after 3 days. Exposure of pituitary cells for 3 days to the inhibin-related peptides transforming growth factor-beta (up to 400 pM) and Müllerian inhibitory substance (up to 100 nM) did not decrease binding of Buserelin, suggesting that the effect was specific to inhibin. Inhibin did not compete with iodinated Buserelin for GnRH-binding sites when they were added to the assay tube simultaneously. In addition, treatment with inhibin halved the number, but did not change the affinity, of GnRH-binding sites and had no effect on either cell number of cell viability. It is concluded that the reduction by inhibin of rat gonadotroph responsiveness to GnRH may be partly related to a decrease in the number of GnRH receptors on the cell surface.

Animals↗
PubMed1988

Pregnant mare's serum gonadotropin stimulates inhibin subunit gene expression in the immature rat ovary: dose response characteristics and relationships to serum gonadotropins, inhibin, and ovarian steroid content.

We have investigated the temporal changes and dose responses of ovarian inhibin gene expression, circulating inhibin, and ovarian estradiol content in PMSG-primed immature female rats. The relative levels of ovarian inhibin alpha- and beta A-subunit messenger RNA (mRNA), serum inhibin, and ovarian steroid content were measured after stimulation of immature female rats with 20 IU PMSG. Each of these variables rose in parallel and peaked at 48 h (relative ovarian inhibin alpha- and beta A-subunit mRNA increased 3.8-fold and 2.8-fold, respectively, serum inhibin 269 U/ml, vs. control 31, P less than 0.01, ovarian estradiol content 114 pmol/pair of ovaries vs. controls 4.7 P less than 0.001), corresponding to the time of maximal follicular development in this animal model. Subsequently each fell to reach a nadir at 96 h. The data are consistent with the hypothesis that PMSG stimulation of inhibin secretion occurs by a mechanism involving inhibin gene transcription. The increase in ovarian inhibin and estradiol synthesis during folliculogenesis and their simultaneous decline before ovulation suggest that 1) the circulating levels of inhibin and estradiol reflect follicular maturation and 2) these two hormones are regulated via a common mechanism during follicular development in the rat.

Animals↗
PubMed1988

Serum inhibin levels in polycystic ovary syndrome: basal levels and response to luteinizing hormone-releasing hormone agonist and exogenous gonadotropin administration.

Serum inhibin levels were measured by RIA twice weekly for 4 weeks in 5 women with the polycystic ovary syndrome (PCOS). These were compared to those in 10 women with normal menstrual cycles. Serum inhibin levels were similar in the 5 PCOS women (mean, 199; range, 126-266 U/L) and were not significantly different from those in the normal women during the early follicular phase (227; 100-485 U/L) or midfollicular phase (243; 143-412 U/L) of their cycles. Inhibin levels were higher (P less than 0.001) in the late follicular phase (408; 227-732 U/L), at midcycle (623; 367-1058 U/L), and during the midluteal phase (1245; 898-1727 U/L) in the normal women compared to those in the PCOS group. Serum inhibin levels were also measured in PCOS (n = 8) and infertile (n = 14) women after the rise and subsequent diminished gonadotropin secretion that occurred during LHRH agonist administration. In both groups, serum LH and FSH increased after initiation of LHRH agonist administration; this increase was accompanied by parallel rises in serum estradiol and inhibin before suppression (PCOS women: r = 0.71; P less than 0.001; n = 108; infertile women: r = 0.42; P less than 0.05; n = 163). All hormone levels, including inhibin, decreased during continued LHRH administration. Five PCOS women underwent ovulation induction using combined LHRH agonist and human menopausal gonadotropin administration. Serum estradiol and inhibin rose in parallel in response to exogenous gonadotropins (r = 0.92; P less than 0.001; n = 77). In conclusion, we found no evidence of a primary defect in ovarian inhibin physiology in women with PCOS in terms of either basal or gonadotropin-stimulated (exogenous or endogenous) secretion.

Adult↗
PubMed1988

Vaginal progesterone administration before ovulation induction with exogenous gonadotropins in polycystic ovarian syndrome.

We studied the value of vaginal progesterone (P4) in suppressing serum LH concentrations and restoring normal luteal phase serum LH concentrations before administration of exogenous gonadotropins in anovulatory women with the polycystic ovarian syndrome (PCOS). P4 (50 mg every 12 h) was administered by vaginal suppository to 9 women (18 cycles) for 14 days before ovulation induction with human menopausal gonadotropin (hMG) and hCG. Serum LH, FSH, estradiol, P4, and PRL levels were measured daily. A biphasic effect on LH secretion occurred during P4 administration. Peak serum LH levels occurred on day 5 (125% of basal levels; P less than 0.05) of vaginal P4 suppository use, followed by a progressive fall (P less than 0.05) to 79% of basal levels, but serum LH levels were still higher than those in normal women despite achieving physiological luteal phase P4 concentrations. Ovulation occurred in 56% of cycles after P4 and hMG/hCG treatment and in 65% of control cycles after hMG/hCG alone. In 7 women, serum LH was measured at 10-min intervals for 6 h before and after vaginal P4 administration for 10 days. LH pulse frequency decreased from 7.4 +/- 1.1 to 4.4 +/- 1.2 pulses/6 h (P less than 0.01), and LH pulse amplitude increased from 3.8 +/- 1.8 to 6.1 +/- 2.9 IU/L (P less than 0.01) after P4 administration. We conclude that vaginal P4 (50 mg every 12 h) 1) produces serum P4 concentrations within the normal range for the luteal phase of the menstrual cycle; 2) elevates serum LH, but not FSH, within 5 days; 3) decreases LH pulse frequency and increases LH pulse amplitude after 10 days, but does not normalize serum LH values; and 5) fails to improve the results of subsequent ovulation induction with exogenous gonadotropins in patients with PCOS.

Administration, Intravaginal↗
PubMed1988

Decreased serum inhibin levels in normal elderly men: evidence for a decline in Sertoli cell function with aging.

Compared to young men, normal elderly men have decreased sperm production despite elevated serum gonadotropin levels. To determine whether the seminiferous tubule defect in elderly men includes decreased Sertoli cell function, we measured serum immunoreactive inhibin concentrations in young and elderly men before and after clomiphene citrate (CC) administration. Thirty-eight healthy men, 19 young (aged 22-35 yr) and 19 elderly (aged 65-85 yr), were studied before CC administration. The mean baseline serum inhibin level was significantly lower (P less than 0.001) in the elderly men than in the young men [416 +/- 22 (+/- SE) vs. 588 +/- 30 U/L], while serum immunoreactive FSH and LH levels were higher in the older men, and bioactive FSH levels were similar in the two age groups. Eleven young men and 13 elderly men were studied after 1 week of CC administration. The mean serum inhibin level increased by 71%, from 566 +/- 36 to 970 +/- 82 U/L, in the young men, but it increased by only 24%, from 421 +/- 26 to 520 +/- 38 U/L, in the elderly men. Serum immunoreactive LH and bioactive and immunoreactive FSH concentrations increased to similar levels in both groups after CC administration. We conclude that the seminiferous tubule defect of elderly men includes decreased Sertoli cell function.

Adult↗
PubMed1988

Serum inhibin concentrations rise throughout normal male and female puberty.

Using a newly developed, sensitive, and specific RIA, we measured the serum concentrations of inhibin, together with those of FSH, LH, and sex steroids, throughout puberty in 99 boys and 102 girls attending a suburban Melbourne school. Serum inhibin levels rose from a geometric mean level of 161 U/L (range, 87-310; 67% confidence interval) at stage I puberty in boys to 442 U/L (range, 300-626) at stage V, while corresponding values in girls were 97 U/L (range, 46-204) and 231 U/L (range, 187-372), respectively. Serum inhibin concentrations were strongly correlated with age and serum FSH, LH, testosterone, and estradiol; all hormones increased in parallel in both boys and girls. After adjustment for age, the partial correlation coefficients remained significant only for testosterone in the boys. We hypothesize that gonadal inhibin production is stimulated by rising gonadotropin levels during pubertal development.

Adolescent↗
PubMed1988

Stimulation of serum inhibin concentrations by gonadotropin-releasing hormone in men with idiopathic hypogonadotropic hypogonadism.

Inhibin is a gonadal hormone thought to be important in FSH regulation. We investigated the effects of the hypogonadotropic state and subsequent GnRH-induced increases in gonadotropin levels on inhibin secretion. Serum levels of inhibin, LH, FSH, and testosterone (T) as well as sperm concentrations were measured in 5 men with idiopathic hypogonadotropic hypogonadism (IHH) before (baseline) and during 8 weeks of GnRH therapy (5 micrograms, sc, every 2 h). Baseline and peak inhibin levels were compared to those in a group of 19 normal men. Before GnRH administration, the mean serum inhibin level was significantly lower in the IHH men than in the normal men [166 +/- 56 (+/- SE) vs. 588 +/- 30 U/L; P less than 0.001]. Serum inhibin levels rose after 1 week of GnRH therapy (P less than 0.05) and remained higher than the baseline level thereafter. The mean peak inhibin level during GnRH administration was lower than the mean value in normal men (485 +/- 166 vs. 588 +/- 30 U/L; P less than 0.05). Serum LH and FSH levels rose promptly to the midnormal range or slightly above it. Serum T levels did not significantly increase until 4-5 weeks of GnRH administration and remained in the low normal range. All IHH men were azoospermic throughout the study. These data are consistent with the hypothesis that inhibin is produced by the testis under gonadotropin control. They also suggest the possibility of defective Sertoli and Leydig cell function in men with IHH, since the men's serum inhibin and T levels did not rise to the same extent as did their normalized serum gonadotropin levels during GnRH administration.

Adult↗
PubMed1988

Follicle-stimulating hormone is required for quantitatively normal inhibin secretion in men.

Inhibin is a glycoprotein hormone produced by the testis and ovary which is postulated to be an important regulator of pituitary FSH secretion. Animal data indicate that inhibin is produced by the Sertoli cells of the testis under the influence of FSH. To determine the role of FSH withdrawal and replacement in the control of inhibin secretion in man, we measured serum inhibin concentrations in men in whom isolated FSH deficiency had been produced by chronic hCG administration; this was followed by FSH replacement. After a 3-month control period, four normal men received hCG for 7 months, resulting in suppression of serum FSH to undetectable levels and urinary FSH excretion to prepubertal levels. Their mean serum inhibin levels fell to 70% of control values during hCG administration [362 +/- 60 (+/- SE) vs. 518 +/- 56 U/L; P less than 0.01]. While continuing hCG, testosterone enanthate was administered for a further 6 months. Serum FSH and inhibin levels remained suppressed to a similar degree. Testosterone administration then was ceased, and hCG continued for a further 2-4 months. Then, while continuing hCG administration, FSH was replaced as either highly purified human FSH (n = 2) or human menopausal gonadotropin (n = 2) for a period of 4-10 months. Serum FSH levels increased to the mid- and upper normal male ranges, respectively. FSH replacement restored serum inhibin levels to 522 +/- 56 U/L (P = NS vs. control). In summary, prolonged selective FSH deficiency induced by chronic hCG administration suppressed inhibin secretion. Replacement of FSH activity restored inhibin secretion to control values. We conclude that 1) FSH is not absolutely required for inhibin secretion in men; and 2) the maintenance of quantitatively normal inhibin secretion requires the combined action of both gonadotropins.

Adult↗
PubMed1988

Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists.

The effects of 31 kDa bovine inhibin on the release of FSH and LH stimulated by gonadotrophin-releasing hormone (GnRH) or its agonist analogue buserelin have been studied using 5-day-old cultures of pituitary cells prepared from adult male Sprague-Dawley rats. Exposure of cultures to increasing concentrations of inhibin for 3 days before and during a 4-h stimulation with GnRH resulted in the progressive suppression of both basal and stimulated gonadotrophin release. At the highest inhibin concentrations FSH release was abolished (inhibin median inhibitory concentration (IC50) = 0.15 U/ml) whereas LH release was suppressed by 75% (IC50 = 0.93 U/ml). To correct for the reduced size of the FSH pool resulting from inhibin pretreatment, the amount of FSH or LH released by an agonist was expressed as a proportion of the total hormone available for release in each case. Following this adjustment, concentrations of inhibin producing maximal effects increased the GnRH median effective concentration for FSH release 4.1-fold and that for LH release 2.2-fold, with inhibin IC50 values of 0.45 and 0.32 U/ml respectively. Inhibin also suppressed the maximum proportion of both FSH and LH that excess GnRH released in 4 h by 36%, with IC50 values of 0.53 and 0.76 U/ml respectively. These effects were not changed by reduction of the inhibin pretreatment period from 3 days to 1 day or by exclusion of inhibin during the stimulation period. After a 3-day pretreatment, inhibin inhibited gonadotrophin release by buserelin less effectively than that by GnRH, but the pattern of antagonism was the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of hypophysectomy on inhibin production by adult rat ovaries: changes in ovarian inhibin gene expression and serum inhibin.

We have investigated the effect of hypophysectomy on adult rat ovarian inhibin alpha- and beta A-subunit mRNA, serum inhibin, and circulating gonadotrophin levels. Immediate declines in ovarian inhibin gene expression and serum inhibin were observed following hypophysectomy, with a nadir on day 4. However, inhibin synthesis determined by these parameters was still apparent at 16 days post-hypophysectomy. Gonadotropin levels were suppressed following hypophysectomy and the fall in inhibin production was highly correlated with disappearance of FSH from the circulation. This study demonstrates that removal of pituitary gonadotropin stimulation results in diminished ovarian inhibin synthesis and provides further evidence indicating that FSH stimulates granulosa cell inhibin synthesis by enhancing inhibin gene transcription.

Animals↗
PubMed1987

The isolation of polypeptides with FSH suppressing activity from bovine follicular fluid which are structurally different to inhibin.

Three proteins (31, 35 and 39 kDa) with inhibin-like activity have been isolated from bovine follicular fluid with identical NH2-terminal amino acid sequences. These polypeptides are distinct from inhibin, based on their different NH2-amino acid sequence, molecular masses, absence of a subunit structure, absence of inhibin immunoactivity and the failure of inhibin antiserum to neutralize their bioactivity in vitro. Their inhibin-like biological activities based on their ability to suppress FSH cell content by pituitary cells in culture are 5-10% of bovine 31 kDa inhibin.

Amino Acid Sequence↗
PubMed1987

Direct inhibition of rat granulosa cell inhibin production by epidermal growth factor in vitro.

The effect of epidermal growth factor (EGF) on inhibin production by rat granulosa cells has been investigated using a recently developed inhibin radioimmunoassay (RIA). Granulosa cells from intact immature diethylstilbestrol (DES)-treated rats were exposed to EGF (1-100 ng/ml) in the presence or absence of FSH for varying periods in vitro. An inhibitory effect of EGF on basal inhibin secretion was evident at day 2 of culture and was sustained over the subsequent 2 days. This action on basal inhibin secretion was dose-dependent, and maximal inhibition to 50% of control was observed at a dose of 100 ng EGF/ml at day 4. EGF also inhibited basal progesterone secretion in a similar manner. EGF caused a dose-dependent inhibition of FSH-stimulated inhibin secretion, with an ID50 (0.5 ng/ml, 0.08 nM) about one-eighth that in the absence of FSH. In addition, EGF also inhibited the stimulation of inhibin production by 8-Br-cAMP and prostaglandin E2. To exclude the possibility that EGF was toxic to the granulosa cells, several biochemical parameters related to cell growth were measured. EGF treatment did not alter cell number but slightly increased [3H]thymidine incorporation into cellular DNA. The effect of EGF on [35S]methionine incorporation into cellular protein was biphasic, being stimulatory at doses less than 10 ng/ml but inhibitory at 100 ng/ml. The present data have demonstrated a direct inhibitory effect of EGF on basal and FSH-stimulated inhibin production by granulosa cells suggesting an important regulatory role of this growth factor in the differentiation of ovarian function.

Animals↗