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Biomedical subjects

W G Rossmanith

Publications and source records attributed to W G Rossmanith.

At least 55 records · Page 3Linked to original sources

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women.

Whereas the nocturnal slowing of the LH pulse frequencies in the early follicular phase (EFP) of the menstrual cycle may be attributed to a sleep-associated increase in opioidergic activity, the concomitant augmentation of LH pulse amplitudes remains unexplained. We reasoned whether alterations in the pituitary gonadotropin responsiveness during the 24-hour rest-activity cycle may account for these enhanced LH pulse amplitudes during sleep. Accordingly, 12 EFP women (cycle days 3-5) were studied on 2 consecutive days during three occasions: a day time between 1000 and 1400 h (day studies), at night between 2200 and 0200 h, while the women were awake (night studies), and finally, during identical night hours, while the women were asleep (sleep studies). At all occasions, blood was collected at 10-min intervals for 4 h, while GnRH (25 micrograms) was administered twice within 2 h. During the day studies, prompt and sustained LH and FSH releases were noted in response to the first and second GnRH stimulations. However, the LH and FSH release after both the first and second GnRH challenges was markedly (P < 0.01) blunted during the night studies. By contrast, this decrease in LH, but not FSH response during the night was completely prevented, when GnRH was administered during sleep. Independent of the time at which GnRH had been administered, the second GnRH stimulations provoked much greater (P < 0.05 or less) LH and FSH releases than the first. Thus, a marked attenuation of the gonadotroph responsiveness is observed in EFP women during the night, and nocturnal sleep may eliminate this decline. Further, the priming actions on the gonadotrophs by repetitive GnRH stimulations are unaffected by the time of GnRH administrations. Collectively, these observations permit us to infer that the increased LH pulse amplitudes observed during sleep in EFP women may not be attributed to increased pituitary responsiveness.

Adult↗

Effects of ovarian surgery on the dopaminergic and opioidergic control of gonadotropin and prolactin secretion in women with polycystic ovarian disease.

Ovarian surgery has been demonstrated as an effective means to establish regular menstrual cycles and resumption of ovulation in patients with polycystic ovarian disease (PCO). We questioned whether such reinstitution of menstrual cyclicity may be associated with changes in the opioidergic and dopaminergic activity known to be aberrant in these women. Opioidergic and dopaminergic tone was therefore assessed in patients with PCO before and after ovarian laser vaporization (n = 4) or classical ovarian wedge resection (n = 4). Blood samples for the determination of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were frequently obtained following opioidergic and/or dopaminergic antagonism affected by naloxone (4 mg i.v.) or metoclopramide (10 mg i.v.). In response to either surgical approach, circulating LH levels decreased (p < 0.01), while FSH concentrations remained unaltered. Further, LH and FSH concentrations did not noticeably change following challenges with naloxone or metoclopramide: this applied to conditions before and after ovarian surgery. Prolactin release in response to metoclopramide was markedly (p < 0.01) higher following ovarian surgery than before. Thus, both ovarian laser surgery and classical wedge resection can effectively restore normal menstrual cyclicity in PCO patients, although they failed to alter opioidergic and dopaminergic activity. Dopaminergic inhibition of prolactin secretion was further enhanced after ovarian surgery. These observations suggest that different modes of ovarian surgery are effective in influencing central gonadal control, but that the central opioidergic and dopaminergic control of gonadotropin and prolactin secretion remains unaffected by ovarian surgery in PCO women, even when menstrual cyclicity is resumed.

Adult↗

Human chorionic gonadotropin secretion from the early human placenta: in vitro regulation by progesterone and its antagonist.

Local actions of placental neurohormones and sex steroids have been proposed to play a role in the regulation of human chorionic gonadotropin (hCG) release from the human placenta. Accordingly, we utilized an in vitro perifusion system and cultures of placental explants to investigate short- and long-term effects of progesterone and its respective antagonist on hCG secretion from the human first-trimester placenta. Tissue slices (100 mg) obtained from legal pregnancy terminations of 9-12 weeks of gestation were continuously perifused and the effluent collected in fractions of 2-20 min. After initial perifusion periods of 30-140 min, either progesterone, a progesterone antagonist (ZK 98-299), or both were added to the perifusion medium at final concentrations of 10(-4)-10(-9) mol/l. Administration was either continuous or intermittent in 10-min pulses. Furthermore, 50-mg pieces of placental explants were cultured in multiwell tissue culture plates for up to 5 days. During the perifusion studies, hCG (determined by enzyme immunoassay) was released in a pulsatile fashion. This hCG pulsatility was decreased in response to both progesterone and progesterone antagonist at all concentrations tested. In contrast, intermittent administration of either treatment increased the hCG secretion. Secretion of hCG was not affected when progesterone and its antagonist were co-administered at equimolar concentrations. These observations demonstrate the diverging effects of progesterone and its antagonist on hCG secretion from the human first-trimester placenta in vitro, depending on the experimental conditions. Thus, progesterone-modulated hCG secretion appears to be regulated in a complex manner, its fine tuning involving other, as yet uninvestigated intraplacental factors.

Abortion, Induced↗

Role of frequency and amplitude of repetitive HCG stimulations for sustained progesterone secretion from the bovine corpus luteum in vitro.

This investigation aimed at evaluating a role for frequencies and amplitudes of repeated HCG stimulations for the optimal maintenance of progesterone (P4) secretion from the bovine corpus luteum in vitro. Slices (100-120 mg) of midluteal bovine corpora lutea were perifused with medium M199 (0.05% BSA, pH 7.2, 38.5 degrees C) and the perifusion effluent collected at 15 minute intervals for 20-29 hours. Unstimulated P4 release (n = 5) was distinctly pulsatile (by Pulsar pulse algorithm), with pulses occurring every 90 +/- 6 minutes (mean +/- SEM) and pulse amplitudes of 14.4 +/- 1.1 ng. Conversely, no pulses were detected in two control perifusions. Unstimulated P4 release increased during the first 5 perifusion hours (from 39.3 +/- 4.6 to 50.3 +/- 5.6 ng/15 min, p less than 0.01), but then appeared to decline (to 29.3 +/- 1.3 ng/15 min, p less than 0.05) towards the end of the perifusion periods. Hourly pulses of HCG (6.7 mM) did not change the P4 pulse amplitudes (16.6 +/- 2.0 ng), the pulse periodicities (105 +/- 15 min) and overall release rates (34.7 +/- 5.7 ng/15 min), nor did they prevent the decline in P4 secretion towards the end of perifusions (n = 5). In contrast, 2-hourly HCG stimulations maintained stable P4 release rates throughout the perifusion periods (34.7 +/- 6.8 ng/15 min), with P4 pulses of similar amplitudes (14.7 +/- 1.7 ng), but of lower periodicities (135 +/- 2 min, p less than 0.05) than during unstimulated conditions (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Episodic thyrotropin (TSH) and prolactin (PRL) secretion during aging in postmenopausal women.

While aging is known to decrease episodic thyrotropin (TSH) secretion in men, no detailed information is available as to age-related alterations in the TSH and prolactin (PRL) release patterns in postmenopausal women (PMW). Accordingly, we compared the TSH and prolactin (PRL) secretory profiles of 6 euthyroid younger PMW (mean age: 53.0 years) with those of 7 euthyroid older PMW (mean age: 80.4 years). In all PMW, blood samples were obtained at 10 minute intervals for 10 hours for serial determinations of TSH and PRL by RIA. While thyroxine (T4) serum concentrations were not different in younger from older PMW, triiodothyronine (T3) levels markedly (p less than 0.05) decreased in older PMW. In both younger and older PMW, TSH and PRL were secreted episodically (by Cluster pulse algorithm), with considerable inter-individual variabilities in either study group. TSH and PRL pulse attributes (interpulse intervals, frequencies, amplitudes) were comparable in younger and older PMW, although a tendency of mean TSH to increase (p = 0.18) was noted for older PMW. Mean TSH and PRL serum concentrations were positively (r = 0.94, p less than 0.01) correlated in older, whereas not in younger PMW. These observations demonstrate that the pulse characteristics of episodic TSH and PRL secretion are preserved in PMW even of old age. However, in view of markedly decreased circulating T3 concentrations and of no substantial change in the TSH pulsatile secretion in older PMW, the negative feedback on the hypothalamic-pituitary unit may be impaired in elderly women.

Aged↗

[Carl Credé: in memory of the 100th anniversary of his death (14 March 1892)].

Major advances taught by the German gynaecologist and obstetrician Carl Siegmund Franz Credé were the manual expression of the placenta and the prophylaxis of the gonoblennorrhoea. Under his supervision, as head of the obstetrical department of the Berlin Charité, the first exclusively gynaecological unit was founded in Europe. In 1856, he was elected head of the Department of Obstetrics of the University of Leipzig. Credé was the editor of the first 42 volumes of "Archiv für Gynäkologie". He died on March 14th, 1892, from prostatic carcinoma.

Germany↗

Role of ovarian sex steroids in the regulation of thyrotropin (TSH) secretion of hypogonadal women.

The exact role of ovarian sex steroids in the neuroendocrine regulation of thyrotropin (TSH) release in women can only be accurately assessed in the absence of any considerable ovarian sex steroid feedback upon the hypothalamic-pituitary unit. Consequently, the unstimulated episodic and thyrotropin-releasing hormone (TRH) stimulated TSH secretion was evaluated in postmenopausal women before and during sequential ovarian sex steroid replacements. Seven euthyroid women (mean age: 59.4 years) were studied initially without any sex steroid replacement (control studies), then on the last day of a 21-day course of oral estradiol-valeriate (E2) administration (2 mg daily) and finally, on the last day of a 21-day course of oral estradiol-progesterone (E2/P4) replacement (2 mg E2 and 200 mg micronized P4 daily). During all study occasions, blood was sampled at 10 min intervals for 10 h, while TRH (200 micrograms iv) was administered 8 h after initiation of blood collections. Compared to the control conditions, serum E2 and P4 concentrations markedly increased (p less than 0.001) following oral E2 or E2/P4 treatments. Total triiodothyronine (T3) and thyroxine (T4) concentrations and free T3 and T4 equivalents remained unchanged during E2 and E2/P4 regimens. In the unstimulated secretory profiles, TSH was found to be episodically released, with little interindividual variability for each study condition. Since the TSH pulse attributes (pulse amplitudes, frequencies, interpulse intervals, mean TSH concentrations, by Cluster pulse algorithm) did not significantly change during E2 and E2/P4 replacements, the episodic character of TSH secretion virtually remained unchanged by sex steroid replacements.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The human first-term placenta in vitro: regulation of hCG secretion by GnRH and its antagonist.

Gonadotropin releasing hormone (GnRH) has been proposed to play a role in the regulation of human chorionic gonadotropin (hCG) release from the human placenta. To test this assumption, we utilized an in vitro perifusion system, together with cultures of placental explants, to investigate short- and long-term effects of GnRH and its respective antagonist on the hCG secretion from the early human placenta. Tissue slices of human placenta (100 mg), obtained from first-trimester terminations of pregnancies, were continuously perifused and the effluent collected in fractions of 2-20 min. After initial perifusion periods of 30-40 min, either GnRH, a GnRH antagonist (SB-75; Asta Pharma, Frankfurt, Germany) or both compounds at equimolar concentrations were added to the perifusion medium at final concentration of 10(-4)-10(-8) mol/l). Administration was effected either continuously or intermittently in 10-min pulses. Further, 50-mg pieces of placental tissue explants were cultured in tissue culture plates for up to 6 days. During the perifusions, hCG (determined by enzymeimmunoassay) was found to be released spontaneously in a pulsatile fashion. Pulse amplitudes and frequencies of this episodic hCG secretion were increased in response to GnRH, but not affected by GnRH antagonist. Also, GnRH stimulated the hCG secretion during cultures of placental explants. When pharmacological doses of GnRH (10(-4) mol/l) were utilized, this stimulatory effect of GnRH was no longer evident, while perifusion with medium containing GnRH antagonist at identical concentrations stimulated the hCG secretion, indicating an intrinsic agonistic activity of the antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

How do androgens affect episodic gonadotrophin secretion in postmenopausal women?

In the absence of any significant ovarian oestrogen secretion, as in post-menopausal women, the hypothalamic-pituitary axis may still be influenced by the androgens which continue to be produced. The episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by postmenopausal women was accordingly assessed following short-term androgen antagonism induced by flutamide, a specific androgen receptor blocker. Blood samples were collected at 10-min intervals for 10 h in nine women before and during flutamide administration (750 mg/day for 6 days) for the determination of gonadotrophin and sex hormone concentrations by radioimmunoassay. On both occasions, 25 micrograms of gonadotrophin-releasing-hormone (GnRH) was injected intravenously 8 h after initiation of the blood collections. Flutamide administration decreased (P less than 0.01 or less) androgen concentrations (testosterone, androstenedione and dehydroepiandrosterone sulphate) in relation to baseline values, but did not alter oestrogen (oestrone and oestradiol) or sex-hormone-binding globulin levels. The LH and FSH pulse characteristics (frequency, amplitude, interpulse interval and transverse mean levels) determined by a cluster algorithm in the gonadotrophin secretory profiles did not differ before and during androgen blockade. By contrast, androgen antagonism increased LH (P less than 0.01) and tended to enhance FSH (P = 0.10) FSH release in response to GnRH stimulation. Hence, short-term androgen receptor blockade with flutamide did not greatly affect episodic gonadotrophin secretion. However, the combined evidence of the enhanced gonadotrophin release observed in response to GnRH stimulation and the unchanged gonadotrophin secretion during androgen antagonism suggests that alterations in the magnitude, but not the frequency, of hypothalamic GnRH release had occurred. Even in the presence of substantial serum androgen concentrations, the gonadotrophin pulse rhythm in hypogonadal women constitutes the maximal-rate GnRH-LH release pattern.

Androgens↗

[Circadian and ultradian rhythms in gonadotropin secretion: regulation by ovarian steroids].

By virtue of the close temporal and functional coupling between intermittent hypothalamic GnRH stimulation and hypophyseal gonadotropin response, assessment of the serum gonadotropin pulsatility and its circadian variations may represent a feasible approach to accurately assess neuroendocrine regulation processes in human reproduction. In the absence of considerable ovarian steroid feedback, as in postmenopausal women, the LH pulsatility with maximal pulse frequencies and amplitudes constitutes an unrestrained basic pulse rhythm. During the menstrual cycle, the pulse characteristics of episodic LH secretion and their circadian excursions undergo characteristic alterations by the changing sex steroid environment. Yet, even during cycle phases of increased oestrogen and progesterone concentrations, the LH pulse frequency is limited to that of the basal rhythm. The LH secretory amplitudes increase from the follicular to the luteal phase, presumably as reflection of an altered pituitary sensitivity to endogenous GnRH stimulation. The tight coupling between the LH signal and the sex steroid response from the corpus luteum emphasizes the importance of central stimulatory rhythms for the target organ. The activity of the central "pulse generator" is profoundly modulated by ovarian steroid feedback and by interactions within the neuroendocrine regulatory units. These regulatory processes have been integrated in a hypothetic model of hypothalamic-pituitary interactions, presumably representing the biochemical basis for the regulation of the central pacemaker.

Animals↗

The impact of ovarian laser surgery on the gonadotrophin secretion in women with polycystic ovarian disease.

To evaluate the effects of ovarian surgery on the deranged episodic gonadotrophin release of women with the polycystic ovarian disease (PCOD), we studied 11 patients with the clinical and endocrinological features of PCOD before and after laparoscopic laser coagulations of ovarian surfaces and cysts. During both occasions, blood was collected at 15-min intervals for 8 h to determine LH and FSH secretory profiles and additionally for 3 h during GnRH injections (25 micrograms twice within 2 h) to assess pituitary responsiveness. Serum testosterone, androstendione and oestrogen (oestrone, oestradiol) levels were markedly reduced (P less than 0.05 or less) after surgery. Mean LH concentrations declined (P less than 0.001), while FSH levels increased (P less than 0.01) following laser treatments. The LH pulse frequencies (by Cluster analysis) did not change after ovarian surgery, but the LH pulse amplitudes were markedly reduced (P less than 0.01). Lower (P less than 0.05 or less) LH concentrations were attained in response to GnRH challenges, and the stimulated FSH release also tended to decrease after laser treatments. Thus, ovarian surgery in PCOD women resulted in reduced serum sex steroid concentrations and in divergent effects on serum LH and FSH levels. The attenuated pituitary LH responsiveness after ovarian surgery suggests action of sex steroids primarily at the pituitary site, while the increase in FSH concentrations may be attributed to other factors selectively modulating FSH release.

Adult↗

Gonadotropin secretion during aging in postmenopausal women.

Although chronological aging is known to result in reduced gonadotropin secretion in women, the precise mechanisms to account for this neuroendocrine manifestation are yet obscure. To evaluate the extent to which the pituitary and/or hypothalamus are involved in the process of aging, we aimed at characterizing the unstimulated and GnRH-stimulated gonadotropin secretion in postmenopausal women (PMW) of different ages. Accordingly, 9 younger PMW (mean age: 53.8 years) in their first and 9 older PMW (mean age: 80.3 years) in their 4th decade of life after natural onset of menopause were studied. In both groups, blood was collected at 10-min intervals for 10 h, while GnRH (25 micrograms i.v.) was administered 8 h after initiation of blood samplings. Compared to younger PMW, basal serum concentrations of dehydroepiandrosterone-sulfate were lower (p less than 0.05) in older PMW, while estrogen (estradiol, estrone), androgen (testosterone, androstendione) and sex hormone binding globulin levels were similar. Lower (p less than 0.01) mean LH levels composed of attenuated (p less than 0.05) LH pulse amplitudes and pulse frequencies (as determined by the cluster pulse algorithm) were found in the 8-hour LH secretory profiles of older PMW. Furthermore, the FSH secretion of older PMW was characterized by lower (p less than 0.01) mean FSH levels with lower (p less than 0.05) FSH pulse amplitudes, but not pulse frequencies. The absolute peak concentrations attained and the total amount of LH and FSH released in response to GnRH stimulations were blunted (p less than 0.001) in older PMW.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

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↗

Autonomous progesterone secretion from the bovine corpus luteum in vitro.

While the regulation of progesterone secretion from the corpus luteum by LH has been convincingly demonstrated, the secretory patterns in the absence of any pituitary LH inputs are yet unclear. Consequently, we investigated the progesterone secretion by an in vitro perifusion system to characterize spontaneous progesterone release from the isolated bovine corpus luteum. Slices (120 mg) of midluteal corpora lutea were placed in perifusion chambers and continuously perifused by Medium-199 for 160-320 min. Progesterone was determined by radioimmunoassay in the effluent fractions collected at 2-min intervals. The spontaneous progesterone release from all bovine corpora lutea was pulsatile. Pulses were observed at mean (+/- SEM) intervals of 17.7 +/- 1.5 min with amplitudes of 6.7 +/- 0.5 ng and release rates of 29.5 +/- 2.4 ng.ml-1.(2 min)-1 (N = 5). Addition of 6.7 nmol/l hCG to the perifusion medium appeared to increase the pulse amplitudes and release rates (195 +/- 25% over unstimulated conditions), but did not change the pulse frequencies (N = 3). Perifusions with calcium-free medium containing 50 mumol/l verapamil and 20 mmol/l EGTA tended to suppress the pulse frequencies and amplitudes of this spontaneous progesterone release, whereas addition of hCG reversed this decrease again (N = 3). When prostaglandin activity was inhibited by 100 mumol/l indomethacin added to the perifusion medium, both pulse frequencies and amplitudes of this progesterone release were enhanced (N = 4). During perifusions with 100 mumol/l of the anti-progesterone ZK 96.734, both the pulse frequencies and amplitudes increased (N = 4). These studies demonstrate an episodic progesterone release from the bovine corpus luteum perifused in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pituitary gonadotropin responsiveness to repeated gonadotropin releasing hormone (GnRH) stimulations in patients with chronic anovulation.

To evaluate whether repeated gonadotropin releasing hormone (GnRH) stimulations were superior to single GnRH administrations for the accurate assessment of pituitary gonadotropin responsiveness, the GnRH-stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses of 49 hyperandrogenic patients (HA) were compared with those of 20 hypogonadotropic patients (HH) and of 24 normally cycling women (N). Blood samples were obtained at frequent intervals during GnRH administrations (25 micrograms twice within 2 h). Unstimulated LH concentrations were higher (p less than 0.001) in HA than in N and HH women. However, basal FSH levels differed only in HA from HH women (p less than 0.001). Following either GnRH stimulation, increased (p less than 0.01) LH and FSH releases were noted in all N, HA and HH women. The GnRH-stimulated LH and FSH responses to either GnRH injections were highest (p less than 0.01) in HA and lowest (p less than 0.01 vs. N) in HH women. The net LH and FSH increases over unstimulated concentrations (delta LH or FSH) in response to either GnRH stimulation were highest (p less than 0.01 or less) in HA women. By contrast, no differences were determined in the delta LH and FSH levels between the first and second GnRH stimulations within each group. These observations document different unstimulated and stimulated gonadotropin concentrations in normal cycling and anovulatory women. Gonadotropin responses to single GnRH administrations differ for anovulatory patients. Since the gonadotropin responses to the second GnRH stimulation are comparable to those during the first GnRH injections, repeated GnRH stimulations may not help to distinguish the degree of pituitary responsiveness in ovulatory from anovulatory women.

Adult↗