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Biomedical subjects

V Padmanabhan

Publications and source records attributed to V Padmanabhan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys.

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.

Adolescent↗
PubMed1997

Circulating concentrations of dimeric inhibin A and B in the male rhesus monkey (Macaca mulatta).

The purpose of this study was to determine the relative concentrations of inhibin A and B in peripheral serum of the adult male rhesus monkey and to examine the testicular contribution to these circulating forms of inhibin. In addition, inhibin B concentrations were also determined in peripheral sera of neonatal and juvenile males and in spermatic vein blood of adults. Immunoradiometric assays specific for the measurement of inhibin A and B were used. These assays also provided an opportunity to reexamine the physiological significance of a replacement infusion of recombinant human (rh)-inhibin A previously employed to study the role of this hormone in regulating FSH secretion in the monkey. In intact adults, the mean (+/-SE) serum concentration of inhibin B was 1008 +/- 184 pg/mL. In contrast, circulating inhibin A concentrations were very low (< 46 pg/mL). Inhibin B was consistently detected in neonatal monkey serum (275 +/- 57 pg/mL), and concentrations of this inhibin dimer increased throughout postnatal development, reaching maximum values in adulthood. Circulating inhibin A concentrations in neonatal and juvenile monkeys were undetectable (< 7 pg/mL). Both forms of inhibin were generally undetectable in castrate sera. The ratio of inhibin B concentrations in testicular venous blood to those in the peripheral circulation was 1.4:1. These findings indicate that, in the male monkey, inhibin B is the principal form of circulating dimeric inhibin, and that this hormone is derived exclusively from the testis. The elevated levels of circulating inhibin B in the juvenile male monkey suggest that, during this phase of development, testicular inhibin B secretion is relatively gonadotropin independent. Additionally, we found that the concentration of circulating inhibin A in castrate animals that had earlier received an iv infusion of rh-inhibin A (832 ng/h/kg BW) was 9881 +/- 2135 pg/mL, indicating that this mode of inhibin replacement may not have been entirely physiological.

Animals↗
PubMed1997

A novel approach to assess changes in endocrine secretion: analysis of GnRH antagonist (Nal-Glu) suppression of gonadotropin release in ovariectomized ewes.

Circulating hormone levels reflect the outcome of multiple feedback systems. A method to accurately assess the dynamics of hormonal changes in samples collected at infrequent intervals and compare these dynamic processes among treatment groups is presented. In this approach, a smooth curve is fitted to each time series of concentrations produced in an experiment, the curves are summarized by numerical measurements, and the measurements are subjected to statistical analysis. The method is demonstrated on data from an experiment that explores the differential effects of a competitive GnRH receptor antagonist (Nal-Glu) on circulating levels of LH and FSH. In this experiment, six adult ovariectomized Suffolk ewes were treated with one of three doses of Nal-Glu using a crossover design. LH and FSH concentrations were determined in hourly samples of jugular blood for 24 h after treatment. Applying the analytical approach, we observed differential effects of increasing concentrations of Nal-Glu on circulating LH and FSH concentrations. The magnitude of LH suppression was similar from dose to dose, while the duration of LH suppression was dose-dependent. In contrast, all doses of Nal-Glu elicited similar effects on the amplitude, duration and time to recovery of FSH suppression. Studies conducted in vitro utilizing dispersed ovine pituitary cells in culture demonstrated that the differential effects of Nal-Glu on FSH and LH secretion were not the outcome of differential sensitivity of FSH and LH to GnRH. The differential effects of Nal-Glu on circulating LH and FSH concentrations may be due to a number of factors, including other releasing or release-inhibiting hormones, paracrine modulators involved in selective regulation of FSH, and/or differences in clearances.

Animals↗
PubMed1996

Invasive intestinal spirochetosis: a report of three cases.

We here report on three patients with gastrointestinal symptoms in whom spirochetes were found in colonic biopsies. The patients, heterosexual adults, were not immunocompromised. Electron microscopy was performed on colonic biopsies from each of the three patients. Apart from the basophilic band consisting of spirochetes, the mucosa was normal in two patients on light microscopy and showed mild inflammation in the other one. However on electron microscopy there was invasion of the colonic epithelial cells, macrophages, goblet cells and Schwann cells by spirochetes, and stunting of the microvilli. The spirochetes conformed to the morphology of Brachyspira aalborgi, and no other infective etiology or pathology could be identified in these patients to account for their symptoms. Since the clinical significance of intestinal spirochetosis is uncertain, antibiotics were not administered to any of the three patients and all three improved symptomatically with non-specific treatment. Intestinal spirochetosis, previously thought to be non-invasive and non-pathogenic in humans, may be invasive and may be the cause of gastrointestinal symptoms in some patients.

Adult↗
PubMed1996

How much of the gonadotropin-releasing hormone (GnRH) surge is required for generation of the luteinizing hormone surge in the ewe? Duration of the endogenous GnRH signal.

The preovulatory LH surge in the sheep is accompanied by a massive and sustained surge of GnRH. The objective of this study was to examine the duration of the endogenous GnRH signal required to induce and maintain a LH surge of full amplitude and duration. For this purpose, we assessed the effect of a competitive GnRH receptor antagonist (Nal-Glu), administered at various times relative to the LH surge, on the development and progression of the surge pattern of LH release. All studies were conducted in a physiological model for the follicular phase of the estrous cycle (artificial follicular phase). In this model, as during the natural follicular phase, the onset of the LH surge is coincident with the initiation of a massive and sustained rise in GnRH secretion. The experimental approach was validated in a preliminary study by determination that the GnRH antagonist could block the LH surge without compromising GnRH release, as measured in pituitary portal blood. In the main experiment, 25 ewes were run through five successive artificial follicular phases, during which the antagonist was not given (control) or was administered before the LH surge, during its ascending limb, or during the descending limb. Treatment with antagonist before the expected time of the surge prevented the LH surge. Treatment during the ascending limb of the LH surge interrupted the rise in LH and caused a prompt cessation of the surge. Treatment during the descending limb of the LH surge resulted in a faster decline in circulating LH concentrations than in control cycles and caused premature termination of the LH surge. Our results are consistent with the conclusion that development and progression of the preovulatory LH surge in sheep depend upon GnRH stimulation throughout its entire time course.

Animals↗
PubMed1996

Use of newly designed microperifusion system with amperometric sensors for near-continuous on-line monitoring of hormone secretion. I. correlation with the luteinizing hormone secretory response to gonadotropin-releasing hormone.

LH is rapidly secreted from the anterior pituitary gland in response to episodic release of GnRH. To understand better the detailed dynamics of this secretory process and related time- and dose-dependent effects, we developed a microperifusion system able to preserve resolution of dynamic secretory responses by minimizing dispersion and with capabilities for automation and continuous on-line monitoring. To monitor secretion at a frequency greater than that feasible with discrete samples, we determined whether LH or another molecule cosecreted by anterior pituitary cells could be monitored on a near-continuous basis using amperometric electrochemical sensors operated under conditions of cyclic voltammetry. The developed culture system incorporated a 32-mu l cell chamber in a controllable constant environment. Miniature sensors were positioned immediately adjacent to the cells to permit differential measurements of the input and effluent streams of medium. With the system, square wave pulses of electrochemically active, biologically inert molecules, e.g. ascorbate and phenol red, showed similar redox profiles before and after the cells, with minimal dispersion. Enzymatically dispersed ovine anterior pituitary cells were cultured on SoloHill glass beads for 4 days, loaded into the chamber, and perifused with DMEM containing 10% FCS for 2 h. After stabilization, the medium was switched to protein-free, HEPES-buffered HBSS with L-glutamine and allowed to flow for a 1-h washout period, followed by GnRH challenges of varying concentrations in a random order. Perifusate was collected in six-drop fractions at approximately 30-sec intervals. Although LH, its individual subunits, and FSH could not be detected amperometrically, GnRH stimulation of the cells simultaneously induced a several log order dose-dependent secretion of both an electrochemically detectable molecule and LH, as measured by RIA. The secretory profiles of the amperometrically detected signal and immunoactive LH were very similar. Dose-response relationships of the amperometric signal and LH to a wide range of GnRH were similar. The responses of both secreted LH and the amperometric signaling molecule(s) to GnRH were triphasic; an initial peak of activity was observed within 20-40 sec, a lower plateau level was observed for the duration of the 4-min GnRH stimulation, and a gradual return to baseline followed. The cells then maintained a constant level of GnRH-independent basal secretion. These results indicate that it is feasible to monitor the complex dynamics of endocrine and cellular responsiveness to secretagogues from endocrine cells/tissues continuously in real-time.

Animals↗
PubMed1996

Age effects of follicle-stimulating hormone and pulsatile luteinizing hormone secretion across the menstrual cycle of premenopausal women.

To characterize the differential aging response in gonadotropin secretion that occurs before menopause, we assessed pulsatile LH and serial FSH, estradiol (E2), and progesterone (P) concentrations in aging women across the menstrual cycle. We conducted 96 daytime studies during the follicular, midluteal, and late luteal phases of the same menstrual cycle in 32 volunteers, aged 40-50 yr (n = 16) and 19-39 yr (n = 16). Mean cycle length was shorter in the older women (26 +/- 0.4 vs. 27.6 +/- 0.6 days; P = 0.02), but mean plasma E2 and P values were similar in the two age groups. Mean plasma FSH was higher in the older group on all 3 study days. For LH, an age difference was observed during the late luteal phase, when mean plasma LH and pulse amplitude were higher in women over 40 yr of age (mean LH, 6.4 +/- 0.7 vs. 3.0 +/- 0.5 IU/L (P = 0.002); mean amplitude, 4.0 +/- 0.5 vs. 2.8 +/- 0.2 IU/L (P = 0.03)]. Pulse frequency was higher in the older group, but not different from that in younger women on all study days. When the subjects aged 35-39 yr were analyzed as a third age group (n = 8), age effects for mean LH persisted, and pulse frequency was higher in the group over 40 yr of age vs. women under age 35 yr (n = 8) in both the follicular phase (7.1 +/- 0.4 us. 5.6 +/- 0.8; P = 0.03) and late luteal phase (5.8 +/- 0.7 vs. 4.4 +/- 0.3; P = 0.03). Although highly variable, individual patterns of gonadotropin secretion in the women over age 40 yr included a sustained elevation in the FSH/LH ratio as well as a failure to demonstrate slow frequency, high amplitude LH pulses in the midluteal phase. In conclusion, 1) the age-related increase in FSH concentrations in ovulatory women, although more pronounced, is associated with phase-dependent enhancement of pulsatile LH secretion; 2) the higher LH concentrations are brought about by changes in both pulse frequency and amplitude; and 3) these age effects preempt overt reductions in cyclic E2 or P concentrations.

Adolescent↗
PubMed1996

Making it happen: the programme. Breaking the rules.

I have always believed that women should be given equal recognition and treatment. My upbringing, observation and experience taught me that I would get nowhere unless I broke the rules. Equal recognition happens only when women are consciously encouraged to reflect and led to understand their worth by looking at their own lives. I use the strategy of sharing my own experience to open dialogue with rural women. For example, in India I helped poor tribal women to go to the Tribal Commissioner when they were being cheated out of tribal rights over land. Appealing to the law makes women stronger, more assertive, and more aware of their rights. Land titles were restored to a few women and they became leaders and supported other women in the same predicament. This change was possible because of a commitment of resources, the attitude of the authorities, and my presence as an Oxfam project officer. As a woman manager I am proud to have helped to create an office environment which in sensitive to women's needs and the way women operate. I have consciously fostered the space for a diversity of ways of working. I can do that because of my management position, and support from other structures, like AGRA and the Gender Unit. It has not been easy as a woman manager in a male dominated, technical program, and as a non-white woman from the South. But with decision-making authority it has been possible to keep women's participation and gender on the agenda.

Developing Countries↗
PubMed1996

Development of a two-site solid-phase immunochemiluminescent assay for measurement of dimeric inhibin-A in human serum and other biological fluids.

Inhibin is a heterodimeric glycoprotein that inhibits the secretion of follitropin from the pituitary and has been isolated in two distinct forms composed of a common alpha subunit and either a beta A or beta B subunit. Utilizing paired monoclonal antibodies specific to the alpha and beta A subunit, we have developed an immunochemiluminescent assay for dimeric inhibin-A. The assay is capable of quantifying free and bound inhibin-A in human serum and follicular fluid. The limit of detection is 10 ng/L. Related proteins exhibit little cross-reactivity or interference. Recovery is excellent. Whereas samples from men and postmenopausal women are near the detection limit of the assay, inhibin-A is higher in the luteal than the follicular phase of normally cycling women, 20-fold higher during in vitro fertilization treatment, and approximately 200-fold greater in pregnancy. The assay measures inhibin-A in follicular fluid from a variety of other species.

Adult↗
PubMed1996

Role of immunophenotyping in characterisation of blast crisis of chronic myeloid leukemia--a study of 25 cases.

The blast cell populations of 25 patients of chronic myeloid leukemia in blast crisis (CML-BC) were studied for morphological, cytochemical and immunophenotypic features. The patients were divided into 6 broad groups based upon the pattern of surface marker positivity-myeloblastic, mixed myeloblastic, megakaryoblastic, mixed lineage, lymphoid and undifferentiated blast crisis. Myeloperoxidase (MPO), Sudan Black B (SBB) and Chloroacetate esterase (CAE) stains showed 100% specificity for the myelomonocytic lineage but the sensitivity was low. Periodic acid Schiff (PAS) stain was neither specific nor sensitive for the lymphoid lineage. Immunophenotyping as compared to morphologic and cytochemical assessment, was seen to be most useful for assigning a lineage to leukemic cells in CML-BC.

Adult↗
PubMed1995

Are immediate early genes involved in gonadotropin-releasing hormone receptor gene regulation? Characterization of changes in GnRH receptor (GnRH-R), c-fos, and c-jun messenger ribonucleic acids during the ovine estrous cycle.

GnRH regulates the secretion and synthesis of gonadotropins by binding to specific receptors located in the plasma membrane of the pituitary gonadotroph. Like the concentration of the signaling ligand GnRH, the number of GnRH receptors (GnRH-R) varies dynamically with the changing endocrine milieu during the ovine estrous cycle. With the recent success in cloning of the mammalian GnRH-R gene, it is becoming increasingly evident that some of the changes in GnRH-R numbers may be mediated at least in part via changes in GnRH-R gene transcription. However, the regulatory steps involved in the GnRH-R transcription are unknown. The present studies were conducted to 1) characterize in detail the changes in GnRH-R gene expression during the 16-day ovine estrous cycle, 2) determine whether or not changes in GnRH-R gene expression during the estrous cycle are paralleled by alterations in the expression of c-fos and c-jun mRNAs, and 3) determine whether GnRH can induce expression of c-fos and c-jun mRNAs. Results revealed that concentrations of GnRH-R mRNA were highest on the day before estrus, when circulating LH concentrations were still low. GnRH-R mRNA concentrations declined steadily starting at 5 h postestrus, the time of the preovulatory LH surge, reaching their lowest levels by 24 h after estrus. Changes in c-jun mRNA levels, in general, paralleled changes in GnRH-R mRNA concentrations, being highest on the day before estrus and declining thereafter. c-Fos mRNA followed a different time course than c-jun mRNA, remaining elevated from Day 8 prior to estrus until the onset of estrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Isolation of nine different biologically and immunologically active molecular variants of bovine follicular inhibin.

A combination of immunoaffinity chromatography, SDS-PAGE, and electroelution was used to simultaneously isolate 0.36-4.65 mg of nine different molecular forms of inhibin (pro alpha C-29 kDa; fully processed 34 kDa; and large inhibin forms 49, 53, 58, 77, 88, 110, and > 160 kDa) from 0.675 L of bovine follicular fluid (bFF). Each inhibin form, except pro alpha C, cross-reacted with inhibin alpha C 1-26-and beta A 82-114-subunit-directed antibodies during immunoblot analysis. Pro alpha C cross-reacted only with alpha-subunit antibodies. The inhibin forms consisted of 22-, 29-, 49-, or 58-kDa alpha subunits and 17- or 58-kDa beta subunits. During cultures of ovine pituitary cells, a 5-ng/ml dose of each inhibin form (except pro alpha C) suppressed basal accumulation of FSH 30% to 50% but increased GnRH-induced LH release 40% to 248%. The various inhibin forms cross-reacted in parallel fashion with standard curves generated during homologous and heterologous RIAs but with markedly different relative immunopotencies. In the RIAs, pro alpha cross-reacted 3- to 18-fold more than the fully processed inhibin form. The fully processed and the seven different large forms of inhibin cross-reacted with different relative immunopotencies in a two-site dimer-specific ELISA. We concluded that 1) a combination of immunoaffinity extraction, SDS-PAGE, and electroelution simultaneously isolated relatively large amounts of highly enriched preparations of nine different molecular forms of immunologically and biologically active inhibin from bFF; 2) eight different dimeric forms of bovine inhibin may regulate both basal FSH and GnRH-induced LH secretion by the pituitary gland, and 3) eight or nine different molecular forms of inhibin cross-react with different relative immunopotencies in the two-site dimer-specific assay or RIAs.

Animals↗
PubMed1995

Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion.

The present studies tested the hypothesis that either short or ultrashort loop negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion occurs in the ewe. As part of ongoing studies investigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment, hypophyseal portal blood was collected from five short-term ovariectomized ewes at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu (10 micrograms/kg body weight). An increase in GnRH pulse frequency in association with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-frequency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release (artificial luteal model). In luteal-phase ewes, administration of Nal-Glu was followed by an increase in GnRH pulse frequency, pulse size and the secretion of GnRH between pulses, and by a blockade of LH release. In ovariectomized ewes treated with estradiol and progesterone, Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our finding that the GnRH antagonist stimulated GnRH secretion is consistent with the hypothesis that endogenous GnRH may influence its own release via either a short or ultrashort loop feedback mechanism.

Animals↗
PubMed1995

Does estradiol induce the preovulatory gonadotropin-releasing hormone (GnRH) surge in the ewe by inducing a progressive change in the mode of operation of the GnRH neurosecretory system.

Estradiol profoundly influences GnRH secretion during the follicular phase of the estrous cycle of the sheep. Estradiol not only regulates the frequency and amplitude of GnRH pulses, but also produces qualitative changes in its pattern of release and induces a sustained GnRH surge during which discrete pulses are not readily evident. In this study, we tested the hypothesis that qualitative changes in GnRH secretion are an integral part of an estradiol-induced change in the mode of operation of the GnRH neurosecretory system that leads to generation of the GnRH surge. This was achieved by the measurement of GnRH in samples of pituitary portal blood collected at 1-min intervals for an 11-h period encompassing the pre- and early surge periods in an artificial follicular phase model. In each of the seven ewes studied, a highly characteristic alteration in the moment to moment pattern of GnRH was observed. This consisted of a progressive change from a strictly episodic pattern of GnRH release to one containing both episodic and nonepisodic components and, after amplification of both components, a period of extremely high values during which individual episodic increases were no longer readily recognizable. Preliminary mathematical modeling of the data suggested that these patterns could be produced by a change in GnRH from a predominantly low to a mixture of low and high amplitude inputs. Similar changes in minute to minute patterns of GnRH secretion were observed during the natural follicular phase. These findings are consistent with the hypothesis that estradiol induces the GnRH surge by altering the mode of neurosecretion, rather than by merely causing quantitative changes in the episodic pattern of release.

Animals↗
PubMed1995

Nature and bioactivity of gonadotropin-releasing hormone (GnRH) secreted during the GnRH surge.

Previous studies have demonstrated a neural action of estradiol in inducing a surge of GnRH in the ewe. However, although the GnRH and LH surges began concurrently, the GnRH surge consistently continued well beyond the surge of LH. Three experiments were conducted to test the hypothesis that the termination of the LH surge results from the secretion of a relatively inactive variant of GnRH during the later phases of the GnRH surge. In the first experiment, hypophyseal portal blood collected during an estrogen-induced LH surge was analyzed for GnRH immunoreactivity using two antibodies having specificity for the N- or C-terminal portion of the GnRH molecule. The duration, amplitude, and time course of the GnRH surge were found to be similar irrespective of the antisera used. In a second experiment, a competitive GnRH antagonist was administered at the beginning of the estrogen-induced GnRH/LH surge at a dose capable of blocking pituitary responsiveness for approximately half the duration of the GnRH surge. Antagonist treatment did not result in any change in the time of onset of the GnRH surge, but there was no increase in LH that naturally occurs coincident with onset of the GnRH surge. Rather, a persistent increase in LH secretion was observed during the latter stages of the GnRH surge, indicating that the GnRH molecules secreted at this time were biologically active. Finally, a sensitive and specific ovine pituitary cell bioassay was used to test bioactivity of GnRH in hypophyseal portal blood during different phases of the GnRH surge. GnRH bioactivity in samples collected early in the GnRH surge was greater than that before the onset of the GnRH surge but no greater than that collected during the descending limb of the surge. The results of all three experiments fail to support the hypothesis that the LH surge ends because of a change in the nature of the GnRH secreted. Rather they show that GnRH secreted throughout the surge is biologically active. Thus, the termination of the LH surge before that of the GnRH surge occurs for reasons other than lack of a bioactive GnRH signal.

Animals↗
PubMed1993

Pituitary glycoprotein hormones in chronic renal failure: evidence for an uncontrolled alpha-subunit release.

Chronic renal failure affects the secretion of pituitary glycoprotein hormones by mechanism(s) that are still unknown. In this study, we evaluated serum concentrations of TSH, free thyroid hormones (FT4, FT3), LH, FSH, testosterone (T), and alpha-subunit (alpha-SU) in 25 uremic patients (19 males and 6 females), both in basal conditions and after stimulatory and inhibitory tests. Basal TSH levels were in the normal range, while FT4 and FT3 were significantly lower than in controls. Basal LH and FSH levels were clearly elevated. The LH levels measured by RIA were significantly higher than those measured by a "two-site" IRMA (48.9 +/- 16.5 vs 18.0 +/- 8.6 U/L) due to alpha-SU cross-reactivity in RIA. FSH bioactivity was normal in all patients. Serum T was normal in all but 3 males, without any correlation with LH and FSH levels. Serum alpha-SU concentrations were significantly elevated (5.5 +/- 3.0 vs 0.4 +/- 0.2 microgram/L). Of 17 patients, the TSH response to TRH was normal in 9 and impaired in 8, whereas alpha-SU response was normal in 5 and impaired in 12. In 8 male patients, TRH plus GnRH caused a normal LH and FSH response in 4 patients, while the increase of alpha-SU was normal in only one patient and significantly lower than expected in subjects with comparable basal alpha-SU levels in the remaining 7. In 2 patients, the combined suppression test with T undecanoate and T3 completely blocked TSH secretion and reduced both LH and FSH release by 30%, while serum alpha-SU levels did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. IV. Follicle-stimulating hormone synthesis and release.

Estradiol-treated, rat pituitary cells were studied to examine the effects of progesterone (P) on follicle-stimulating hormone (FSH) synthesis and secretion. Progesterone was administered prior to or concurrent with 3 h secretory challenges with either gonadotropin-releasing hormone (GnRH), the iontophore A23187, the protein kinase C activator phorbol 12,13-myristate (PMA), or no secretagogue. Medium FSH levels and cell FSH stores were quantified by radioimmunoassay and bioassay. Acute (< 6 h) exposures to P increased medium levels of immunoreactive and bioactive FSH following GnRH challenge without influencing total (cell + medium) values whereas chronic (9-24 h) treatments increased both parameters. Chronic P elevated total FSH levels even when no secretagogue was present. Studies with antiprogestins, 5 alpha-dihydroprogesterone and 5 alpha-reductase inhibitors revealed that this direct action of P depended on progestin receptor occupation but not on 5 alpha-reduction. These studies indicate that P selectively increases bioactive and immunoactive FSH levels, presumably by increasing FSH synthesis, and characterize the time course and cellular mechanisms of this response. To accommodate for P modulation of total FSH levels, FSH secretion was standardized as the percentage of cellular stores available for release. Progesterone modulation of GnRH-stimulated FSH secretion was multiphasic, i.e. increased at 0-6 h, unchanged at 9 h and suppressed at 24 h. Acute and chronic exposures to P similarly modulated A23187-stimulated FSH release, whereas both P treatments increased PMA-stimulated FSH secretion. In these experiments P modulated luteinizing hormone secretion in parallel fashion, suggesting that common cellular mechanisms underlie peptidergic and steroidal regulation of the secretion of both gonadotropins.

Animals↗