| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Departments of Cell Biology and Physiology (S.R., T.M.P.) and Medicine (S.J.W.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; Duquesne University School of Health Sciences (C.R.P.), Pittsburgh, Pennsylvania 15282; and the Medical Research Council Reproductive Biology Unit, University of Edinburgh (A.S.M.), Edinburgh, United Kingdom EH3 9EW
Address all correspondence and requests for reprints to: Dr. Tony M. Plant, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, S330 Biomedical Science Tower, Pittsburgh, Pennsylvania 15261.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-C levels during the
experiment. Normal pulsatile activity in the
hypothalamic-pituitary-Leydig cell axis was confirmed by monitoring
changes in circulating concentrations of LH and T in 12-h windows of
sequential blood collection (1200–2400 h; every 20 min) before,
during, and after the rh inhibin A and vehicle infusions. Although
infusion of rh inhibin A, which led to a 12 ng/ml square wave increment
in circulating levels of this inhibin dimer, produced a marked decline
in circulating FSH concentrations, significant suppression of the
secretion of this gonadotropin was not manifest until 54 h after
initiation of the infusion. Despite the marked decline in FSH secretion
during the last 24 h of the 4-day infusion of recombinant hormone,
circulating inhibin B and pro--C concentrations were maintained at
preinfusion control levels (1 ng/ml). The finding that imposition of an exaggerated circulating inhibin signal led to suppression of FSH secretion in the male monkey only after 2 days of exposure to the hormone indicates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged. Moreover, as the decrease in FSH did not lead to changes in native inhibin secretion, it seems reasonable to propose that the FSH-inhibin feedback loop that governs testicular function in higher primates operates with considerable hysteresis at both the pituitary and gonadal levels. The failure of dramatically elevated inhibin A levels to influence the pulsatile secretion of LH in the monkey reinforces the idea that in this species the pituitary action of testicular inhibin is specific for FSH and does not involve modulation of GnRH receptor levels.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The time course of inhibin’s action to suppress FSH secretion in the monkey, however, remains uncertain. Single injections of 50–200 µg rh inhibin A to either castrated male or intact female macaques have failed to suppress FSH secretion (6, 7). On the other hand, twice daily sc injections of the recombinant hormone (60 µg/injection) during the follicular phase of the rhesus monkey resulted in a suppression of circulating FSH levels (8).
To understand further the dynamics of the action of inhibin at the
level of the gonadotroph of the primate pituitary, a study of the time
course of suppression of FSH secretion in response to an increase in
circulating inhibin in intact male rhesus monkeys was initiated.
Although inhibin B is now known to comprise the circulating form of
testicular inhibin in this species (9), only inhibin A was available in
sufficient quantities at the time this study was initiated in 1995.
Accordingly, five animals received a continuous iv infusion of rh
inhibin A for 96 h with the aim of doubling circulating
immunoactive inhibin concentrations, which was to be confirmed using
the Monash RIA (10). In addition, a specific enzyme-linked
immunosorbent assay (ELISA) for the measurement of inhibin A allowed
the inhibin signal achieved by the infusion of recombinant hormone to
be determined more precisely. Changes in circulating FSH concentrations
effected by inhibin treatment were monitored employing a new homologous
macaque FSH RIA. Lastly, the availability of specific ELISAs for other
forms of inhibin provided an opportunity to characterize changes, if
any, in the circulating concentrations of pro--C and inhibin B
effected by the infusion of rh inhibin A.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Access to venous circulation
To withdraw blood samples and to infuse inhibin with minimal
restraint and without tranquilization, the monkeys were implanted with
two venous catheters and housed in remote sampling cages, as described
previously (5). Postsurgically, the animals received a single im
injection of penicillin (300,000 U; Bicillin L-A, Wyeth Laboratories,
Philadelphia, PA), and a broad spectrum antibiotic (100 mg, iv,
cefazolin sodium; Kefzol, Apothecon, Princeton, NJ) and an analgesic,
meperidine hydrochloride (1 mg/kg BW, iv; Demerol, Elkins-Sinn, Cherry
Hill, NJ), twice daily for 4 days. The catheters, swivels, and related
accessories were silanized to minimize adsorption of the recombinant
hormone during infusion, as described previously (5). The animals were
allowed to adapt to the infusion and withdrawal system for a minimum of
3 weeks before the initiation of the study. The patency of the
catheters was maintained by a continuous infusion of heparinized saline
[3 ml/h, 4 U heparin (Elkins-Sinn)/ml isoosmolar NaCl (Abbott
Laboratories, North Chicago, IL]. The animals were sedated at weekly
intervals with ketamine hydrochloride (100 mg/animal, iv; Ketaject,
Phoenix Pharmaceuticals, St. Joseph, MO) to examine cutaneous fistulas
and other dermal areas under the jacket for indications of infection or
irritation. Jacket inspections were not conducted during experimental
infusions.
Collection of blood samples
Blood samples (1.5–2 ml) were drawn in heparinized syringes and
collected in sterile tubes. During frequent sampling (20- to 120-min
intervals), plasma was separated, and the cells were suspended in
heparinized saline and returned at regular intervals to the respective
animal. Plasma was stored at -20 C until required for assays. The
details of blood sampling schedules are described in Experimental
design below.
Inhibin infusate
It was previously established that, after castration in the male
rhesus monkey, a constant iv infusion of 832 ng rh inhibin A/h·kg
maintained circulating immunoactive inhibin concentrations at
precastration control levels of approximately 2 ng/ml (5). In the
present study, a similar dose of rh inhibin A (832 ng/h·kg) was
selected for infusion with the aim to double the circulating
immunoactive inhibin levels in intact male monkeys. It should be noted,
however, that one monkey received only 748.5 ng/h·kg.
The rh inhibin A (1 mg/ml in 0.1% trifluoroacetic acid in
acetonitrile) used in the current study was obtained from Biotech
Australia (Roseville, Australia), and the characteristics of the
hormone have been described previously (11). Custom rh inhibin A
infusates were prepared for each animal in silanized glassware using
Dulbecco’s PBS, pH 7.4, containing the stock solution (
4.5 µl/ml),
cefazolin sodium (0.2 mg/ml), and serum (1%) taken earlier from the
monkey that was to receive the infusion, as previously described (5).
The infusates were dispensed into 60-ml fractions and frozen within 30
min of preparation. The vehicle infusates, containing the appropriate
concentration of 0.1% trifluoroacetic acid in acetonitrile in
Dulbecco’s PBS, were prepared as described above for the inhibin
infusates. Fractions of the infusates were thawed each night at 4 C in
readiness to replenish the infusion reservoir in the morning.
Assays
FSH. Plasma FSH was measured using new homologous RIA
reagents supplied by the National Hormone and Pituitary Program.
Recombinant cynomolgus FSH (NICHHD Rec-MoFSH-RP-1, AFP 6940A) was
employed for the reference preparation and the radioiodinated tracer,
and a polyclonal rabbit antiserum (AFP782594) raised against
recombinant cynomolgus FSH was used as the first antibody.
Gonadotropin-free serum (200 µl/tube) was added to the standard
curve, and unknowns were assayed at this volume. The ED50
of the assay was 0.06 ng AFP 6940A/tube, which is equivalent to 1.3
ng/tube WP-XIII-21–42, the FSH standard used in the earlier
heterologous FSH RIA (12). The cross-reactivities with recombinant
cynomolgus LH (AFP-6936A) and common -subunit (AFP-5679A-SIAFP) were
less than 0.02% and less than 0.01%, respectively. The minimal
detectable dose was 0.006 ng/tube. The intra- and interassay
coefficients of variation were less than 5% and 8%, respectively.
LH. Plasma LH was estimated using a RIA kit supplied by the National Hormone and Pituitary Program. It consists of a cynomolgus LH:anti-hCG (rabbit 13, pool D) RIA system that uses a rhesus pituitary LH preparation (NICHHD rh LH RP-1) as standard (13). The average sensitivity of the LH assay was 7.5 ng NICHHD rh LH RP-1/ml, and the intra- and interassay coefficients of variation of this assay were less than 4% and 13%, respectively.
Immunoactive inhibin. Plasma inhibin concentrations were measured, as described previously (14), using a double antibody RIA, with rh inhibin A as standard (0.03–0.3 ng/tube; Biotech Australia), purified bovine inhibin as the iodinated tracer, and an antiserum to bovine 31-kDa inhibin (no. 1989) obtained from Dr. David Robertson through the Contraceptive Development Branch, NICHHD. The intraassay coefficient of variation in the midportion of the standard curve was always less than 10%. The interassay coefficients of variation (n = 5 assays) of samples of various potencies ranged from 10.6–19.6%.
Inhibin A and B. Dimeric inhibins were measured by two-site
ELISAs, previously described in detail (15, 16) and used by us to
measure the circulating concentrations of these hormones in the male
rhesus monkey (10). Briefly, the ELISA for inhibin A uses rh inhibin A
(Genentech, South San Francisco, CA) as the standard and two monoclonal
antibodies: clone R1, directed toward the inhibin -subunit, and
clone E4, directed toward the inhibin ßA-subunit (17). In the ELISA
for inhibin B, a monoclonal antibody specific to the ßB-subunit (C5)
was used for capture, and the F(ab) fraction of a mouse monoclonal
antibody (R1) conjugated to alkaline phosphatase, used in the inhibin A
ELISA, was used for detection. The sensitivities of the ELISAs for
inhibin A and B were 7 and 8 pg/ml, respectively, and the coefficients
of variation for these assays were 8.5% and 6.1%, respectively.
Pro--C. Plasma levels of pro--C were measured using a
two-site ELISA exactly as described previously (18) with the monoclonal
antibody, INPRO13, directed to the pro region of inhibin as capture
antibody, and the F(ab) alkaline phosphate substrate conjugate of
monoclonal R1 to the -C-subunit of inhibin for detection. A
pro--C preparation purified from human follicular fluid was used as
the standard, as described previously (18). The sensitivity of the
assay was 20 pg/ml. Serial dilutions of plasma from intact juvenile and
adult male monkeys were linear with the human pro--C standard. The
recovery of pro--C standard between 50–200 pg spiked into plasma
from juvenile monkeys was between 93–105%. The coefficient of
variation was 9.7%.
Testosterone (T). Plasma T was assayed in duplicate by a previously described RIA (19) that employs antiserum T3–125 (Endocrine Sciences, Tarzana, CA). The mean sensitivity of the assay was approximately 0.1 ng/ml. The intraassay and mean interassay coefficients of variation were 7.8% and 12.3%, respectively.
Experimental design
Five intact adult male rhesus monkeys received an iv infusion of
rh inhibin A (748–832 ng/h·kg) followed, after an interval of
approximately 4 weeks, by the vehicle infusion. Before initiating the
infusion of rh inhibin A, a typical pattern of pulsatile activity in
the pituitary-Leydig cell axis was established for each monkey by
monitoring moment to moment changes in the circulating concentrations
of T from 1200–2400 h. This 12-h window was selected because it
provides a representative profile of the pulsatile activity in the
pituitary-testicular axis (20). Later, the pulsatile profile of LH was
also determined in the samples collected during this 12-h window.
One to 2 weeks later, the rh inhibin A infusion was initiated. At this time, the infusion line was first exposed for 60 min to 1% serum in Dulbecco’s PBS (2 ml/h) to minimize subsequent adsorption of the recombinant hormone. The rh inhibin A infusion, also at a rate of 2 ml/h, was then started at 0 h between 0900–0930 h. It should be noted, however, that the animals did not immediately begin to receive the rh inhibin A because of a dead space of approximately 2 ml in the infusion line. The hormone infusion was terminated after 96 h. The changes in circulating FSH concentrations effected by rh inhibin A infusion were monitored in blood samples collected 60, 30, and 5 min before and at 6-h intervals during the 96-h infusion. An additional sample was collected 6 h after termination of the infusion. The foregoing samples together with those collected 0.5, 1.0, 1.5, 2.0, and 4.0 h immediately after both the initiation and the termination of the inhibin infusion were assayed for circulating concentrations of immunoactive inhibin and inhibin A.
In addition, on the fourth day of rh inhibin A infusion, a series of frequent blood samples was collected in a 12-h window (75–87 h of infusion), as described above. The primary purpose of this analysis was to examine the effects, if any, of the inhibin infusion on the pulsatile activity of the LH-T axis.
After the collection of the postinfusion sample at 102 h, the inhibin infusate that remained in the line was removed by aspiration, thus eliminating any further delivery of the hormone. At this time, a continuous heparinized saline infusion was reestablished. Approximately 1 week after the termination of the inhibin infusion, a final 12-h window of blood sampling was performed to monitor the postinfusion moment to moment changes in the pulsatile patterns of LH and T secretion. During this window, additional samples were collected at 0, 6, and 12 h to establish the postinfusion recovery in the concentrations of FSH and inhibin.
The blood-sampling schedules during vehicle infusion were identical to those described for the rh inhibin A infusion. It should be noted here that in one monkey, the patency of the infusion line was lost toward the end (77–96 h) of vehicle treatment.
LH and T pulse detection
Episodes of LH and T secretion, i.e. pulses, during
each of the 12-h (1200–2400 h) windows of sequential sampling were
identified by a pulse detection algorithm (21) that determines the
number (frequency) and quantitates the amplitude of the hormone pulses.
The G values used, which produce a 1% false positive rate, were: G(1)
= 4.4, G(2) = 2.6, G(3) = 1.96, G(4) = 1.46, and G(5) = 1.13. For
purposes of calculation, the respective assay limit of detection was
substituted for undetectable samples.
Statistical analyses
The significances of differences in mean hormone concentrations
before, at 6-h intervals during, and after inhibin or vehicle infusion
were determined by two-way ANOVA with repeated measures. The effects of
treatment over time were tested by one-factor ANOVA with repeated
measures followed by Duncan’s new multiple range test. A preinfusion
value was obtained for each hormone by averaging the concentrations of
the three samples collected before infusion. Additionally, the
significance of differences among mean pulse frequency, amplitude, and
concentration of LH and T during 12-h windows of frequent sampling
before, during, and after inhibin and vehicle infusion were assessed as
described above. Hormone levels below the sensitivity of the assays
were assigned a concentration equivalent to the minimum detectable
concentration in the respective assay.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
. Initiation
of the rh inhibin A infusion resulted, after a short delay due to
catheter dead space, in a square wave increase in immunoactive inhibin
concentrations in the circulation that plateaued after 12 h at a
value of approximately 7 ng/ml for the remainder of the duration of the
infusion. After termination of the hormone infusion at 96 h, the
mean concentration of immunoactive inhibin declined rapidly to reach,
within 60 min, the preinfusion level (Fig. 1). Infusion of the vehicle
did not affect circulating immunoactive inhibin concentrations.
|
). Quantitative differences were observed, however; circulating
inhibin A concentrations increased from very low levels (0.05 ng/ml)
to plateau at approximately 12 ng/ml, whereas immunoactive inhibin rose
from approximately 2 to 7 ng/ml. Immediately after termination of the
inhibin infusion, the declines in immunoactive inhibin and inhibin A
levels were parallel. Six hours later, however, circulating inhibin A
levels, but not those of immunoactive inhibin, remained notably higher
than those observed before the infusion (Fig. 1). Moreover, measurable
concentrations of inhibin A (
0.30 ng/ml) persisted in the
circulation 1 week after the termination of hormone infusion (data not
shown).
The changes in mean circulating FSH concentrations effected by the
increase in circulating inhibin levels are also shown in Fig. 1. During
the initial 24 h of inhibin treatment, the circulating FSH
concentrations were indistinguishable from those after vehicle
treatment. Thereafter, FSH levels declined progressively and
significantly from approximately 0.13 ng/ml to reach, at 72 h, a
stable low level of 0.05 ng/ml, which was maintained over the final
24 h of infusion. This suppression of FSH persisted for the 6
h of sampling that followed termination of the inhibin infusion (Fig. 1). When FSH levels were next monitored 1 week later, levels of this
gonadotropin had rebounded to preinfusion levels (data not shown).
Moment to moment changes in LH and T concentrations during the last day
of the inhibin infusion, when FSH secretion was maximally suppressed,
appeared indistinguishable from those before and after the recombinant
hormone treatment and those during vehicle infusion (Fig. 2). This impression was confirmed by
statistical treatment of the formal analysis of the pulsatile hormone
profiles using the algorithm, Pulsar (Table 1). Specifically, no significant
differences were evident in the mean LH or T pulse frequencies and
pulse amplitudes in 12-h windows of frequent sampling before, during,
and after inhibin treatment; similarly, integrated LH or T
concentrations were also statistically indistinguishable at these times
(Table 1).
|
|
-C
throughout the infusion of rh inhibin A were unremarkable (Fig. 3).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Assessment of the physiological significance of the increment in circulating inhibin A levels achieved in the infused animals is further confounded by the fact that, in the monkey, testicular inhibin is accounted for almost exclusively by inhibin B, which in intact adult males circulates at a concentration of approximately 1 ng/ml (9). Therefore, the circulating inhibin A levels that were produced by the infusion of the recombinant hormone (10–15 ng/ml) were markedly greater than those of native monkey inhibin B. Thus, the full significance of the present experiment cannot be determined until the relative biopotencies of native monkey inhibin and rh inhibin A have been established. In this regard, it is of interest to note that the in vitro sensitivity of the gonadotroph to rh inhibin B appears to exhibit species specificity. Namely, FSH production is markedly suppressed by inhibin B in pituitary cell cultures from rats, but not in those from sheep (22). Notwithstanding the foregoing uncertainties, the present findings demonstrate that in the adult male monkey, a representative higher primate, FSH secretion is inhibited by an increase in plasma inhibin concentrations. Moreover, insofar as the infusion of recombinant hormone employed appeared to provide the gonadotroph of the monkey with a substantial inhibin stimulus, the delay of 48 h before circulating FSH concentrations were reduced demonstrates that in this species, the feedback action of this testicular hormone on FSH secretion is heavily lagged.
A more rapid (within 2–8 h) suppression of FSH levels was observed, however, after sc injection of a large bolus of rh inhibin A (60 µg/kg) during the follicular phase of the menstrual cycle in the monkey (8). In the intact adult and castrated male rat, a similar rapid suppression of FSH secretion (within 2–10 h) after a bolus dose of rh inhibin A (10–100 µg/kg) has also been reported (24, 25, 26). Although no suppression of FSH was observed after iv injection of 50 µg rh inhibin A into castrated male macaques (6), the relatively rapid suppression of FSH secretion that has generally been reported after the administration of large bolus doses of rh inhibin A to rats and monkeys probably reflects the consequence of the very high circulating concentrations of inhibin that would be expected after this mode of hormone treatment. It is unlikely that this generalization applies to all species, for in the castrated ram, continuous iv infusion of rh inhibin A at a rate comparable to that employed in the current study resulted in the suppression of FSH secretion within 6–12 h (27, 28). From the foregoing discussion, it is difficult to arrive at a consensus regarding the comparative dynamics of inhibin’s action on pituitary FSH secretion.
In contrast to the suppression of FSH secretion induced by inhibin infusion in the male rhesus monkey, this exaggerated and protracted feedback signal was without effect on pulsatile LH secretion assessed either directly by RIA of the gonadotropin or indirectly by monitoring the testicular T response. This finding strongly reinforces the idea that testicular inhibin selectively regulates FSH secretion in the monkey (3, 4, 5, 12) and, by inference, has little effect on either hypothalamic GnRH secretion or pituitary GnRH receptor expression in this species. In this regard the sheep and monkey may be similar. Studies of the castrated ram have indicated that inhibin administration in vivo does not alter LH secretion (27, 28), and in the ewe, treatment with either ovine or bovine follicular fluid, which produced a marked inhibition of FSH secretion, had no discernible effect on GnRH receptor gene expression (29, 30). Interestingly, in cultured ovine pituitary cells, inhibin increased GnRH receptor binding (31, 32) and mRNA levels (33) and augmented GnRH-stimulated LH release (31, 32). In the rat, the situation appears to be different. Although many in vivo studies have found that bolus injections of inhibin do not alter GnRH secretion (34) or spontaneous or GnRH-induced LH secretion (24, 25, 26, 35), a recent investigation showed that a prolonged infusion of rh inhibin A (6 µg/kg·h, for 72 h) reduced LH secretion in immature male rats (36). Moreover, in the latter study the inhibin-induced LH suppression was associated with a marked decrease in GnRH receptor mRNA levels, a finding consistent with results obtained from experiments with rat pituitary cell cultures indicating that inhibin decreases the number of GnRH-binding sites (37, 38), blocks GnRH-stimulated GnRH receptor synthesis (39), and suppresses GnRH-induced LH secretion (35, 38, 40).
The present study also provided the opportunity to examine the temporal
relationship between a decrease in FSH concentrations and the secretion
of testicular inhibins. The circulating levels of inhibin B and
pro--C levels observed in this study (1 ng/ml of each) were similar
to those previously reported for this macaque (9, 41, 42). Although
circulating concentrations of FSH were significantly suppressed during
the last 48 h of rh inhibin A infusion, native inhibin B and
pro--C levels were maintained at control levels for the duration
of the treatment. Interestingly, in normal men, suppression of
gonadotropin secretion with T enanthate led to a decline in plasma
inhibin B concentrations that did not appear until 2 days after a
significant inhibition of FSH secretion was established (43). A latency
in stimulating testicular inhibin B secretion in normal men was also
observed when the FSH drive was enhanced by injection of the
recombinant gonadotropin (44). Although the dynamics of the inhibin B
response to increased FSH stimulation have not been directly studied in
the monkey, immunoactive inhibin levels also rose slowly after
pulsatile administration of this gonadotropin (45). Thus, it would seem
reasonable to conclude that the FSH-inhibin feedback loop in higher
primates operates with considerable hysteresis at both the pituitary
and gonadal levels and, as such, contrasts with the more dynamic
control system regulating Leydig cell function.
Lastly, a paracrine and/or autocrine role for inhibin in modulating Leydig cell steroidogenesis has been suggested by some investigators (46). In the present study, however, in which circulating inhibin A levels in excess of 10 ng/ml were achieved for a duration of 96 h, there was no evidence to indicate modulation of testicular T stimulation in response to the spontaneous pulsatile profile of endogenous LH secretion.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received January 13, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-C-containing
forms in human serum by a new ultrasensitive two-site enzyme-linked
immunosorbent assay. J Clin Endocrinol Metab 80:2926–2932-C in the plasma of neonatal, juvenile and adult
male rhesus monkeys. 79th Annual Meeting of The Endocrine Society,
Minneapolis MN, 1997 (Abstract P2–337)
This article has been cited by other articles:
 |
|
 |
|
  E. D. Albrecht, M. V. Lane, G. R. Marshall, I. Merchenthaler, D. R. Simorangkir, C. R. Pohl, T. M. Plant, and G. J. Pepe Estrogen Promotes Germ Cell and Seminiferous Tubule Development in the Baboon Fetal Testis Biol Reprod, August 1, 2009; 81(2): 406 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Robertson, G. E. Hale, D. Jolley, I. S. Fraser, C. L. Hughes, and H. G. Burger Interrelationships between Ovarian and Pituitary Hormones in Ovulatory Menstrual Cycles across Reproductive Age J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 138 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Guo, S.-X. Tao, M. Chen, Y.-Q. Shi, Z.-Q. Zhang, Y.-C. Li, X.-S. Zhang, Z.-Y. Hu, and Y.-X. Liu Heat Treatment Induces Liver Receptor Homolog-1 Expression in Monkey and Rat Sertoli Cells Endocrinology, March 1, 2007; 148(3): 1255 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Seminara, M. J. DiPietro, S. Ramaswamy, W. F. Crowley Jr., and T. M. Plant Continuous Human Metastin 45-54 Infusion Desensitizes G Protein-Coupled Receptor 54-Induced Gonadotropin-Releasing Hormone Release Monitored Indirectly in the Juvenile Male Rhesus Monkey (Macaca mulatta): A Finding with Therapeutic Implications Endocrinology, May 1, 2006; 147(5): 2122 - 2126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. S. Devi, K. Sarda, B. Stephen, P. Nagarajan, and S. S. Majumdar Follicle-Stimulating Hormone-Independent Functions of Primate Sertoli Cells: Potential Implications in the Diagnosis and Management of Male Infertility J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1062 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Plant, S. Ramaswamy, and M. J. DiPietro Repetitive Activation of Hypothalamic G Protein-Coupled Receptor 54 with Intravenous Pulses of Kisspeptin in the Juvenile Monkey (Macaca mulatta) Elicits a Sustained Train of Gonadotropin-Releasing Hormone Discharges Endocrinology, February 1, 2006; 147(2): 1007 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ramaswamy Pubertal Augmentation in Juvenile Rhesus Monkey Testosterone Production Induced by Invariant Gonadotropin Stimulation Is Inhibited by Estrogen J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5866 - 5875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Marshall, S. Ramaswamy, and T. M. Plant Gonadotropin-Independent Proliferation of the Pale Type A Spermatogonia in the Adult Rhesus Monkey (Macaca mulatta) Biol Reprod, August 1, 2005; 73(2): 222 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Ramaswamy, C R Pohl, G R Marshall, and T M Plant A switch from continuous to episodic testicular testosterone release in response to pulsatile LH stimulation in juvenile rhesus monkeys (Macaca mulatta) J. Endocrinol., October 1, 2004; 183(1): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M S Medan, S Akagi, H Kaneko, G Watanabe, C G Tsonis, and K Taya Effects of re-immunization of heifers against inhibin on hormonal profiles and ovulation rate Reproduction, October 1, 2004; 128(4): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Okada, A. Murota-Kawano, S. S. Kakar, and S. J. Winters Evidence that Gonadotropin-Releasing Hormone (GnRH) II Stimulates Luteinizing Hormone and Follicle-Stimulating Hormone Secretion from Monkey Pituitary Cultures by Activating the GnRH I Receptor Biol Reprod, October 1, 2003; 69(4): 1356 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Zachos, R. B. Billiar, E. D. Albrecht, and G. J. Pepe Developmental Regulation of Follicle-Stimulating Hormone Receptor Messenger RNA Expression in the Baboon Fetal Ovary Biol Reprod, May 1, 2003; 68(5): 1911 - 1917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ramaswamy, G. R. Marshall, C. R. Pohl, R. L. Friedman, and T. M. Plant Inhibitory and Stimulatory Regulation of Testicular Inhibin B Secretion by Luteinizing Hormone and Follicle-Stimulating Hormone, Respectively, in the Rhesus Monkey (Macaca mulatta) Endocrinology, April 1, 2003; 144(4): 1175 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Padmanabhan, M. B. Brown, G. E. Dahl, N. P. Evans, F. J. Karsch, D. T. Mauger, J. D. Neill, and J. Van Cleeff Neuroendocrine Control of Follicle-Stimulating Hormone (FSH) Secretion: III. Is There a Gonadotropin-Releasing Hormone-Independent Component of Episodic FSH Secretion in Ovariectomized and Luteal Phase Ewes? Endocrinology, April 1, 2003; 144(4): 1380 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Narula, Y.-Q. Gu, L. O'Donnell, P. G. Stanton, D. M. Robertson, R. I. McLachlan, and W. J. Bremner Variability in Sperm Suppression during Testosterone Administration to Adult Monkeys Is Related to Follicle Stimulating Hormone Suppression and Not to Intratesticular Androgens J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3399 - 3406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kawakami, Y. Fujii, Y. Okada, and S. J. Winters Paracrine Regulation of FSH by Follistatin in Folliculostellate Cell-Enriched Primate Pituitary Cell Cultures Endocrinology, June 1, 2002; 143(6): 2250 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Padmanabhan, D. Battaglia, M. B. Brown, F. J. Karsch, J. S. Lee, W. Pan, D. J. Phillips, and J. Van Cleeff Neuroendocrine Control of Follicle-Stimulating Hormone (FSH) Secretion: II. Is Follistatin-Induced Suppression of FSH Secretion Mediated via Changes in Activin Availability and Does It Involve Changes in Gonadotropin-Releasing Hormone Secretion? Biol Reprod, May 1, 2002; 66(5): 1395 - 1402. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. M. Plant and G. R. Marshall The Functional Significance of FSH in Spermatogenesis and the Control of Its Secretion in Male Primates Endocr. Rev., December 1, 2001; 22(6): 764 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Hayes, N. Pitteloud, S. DeCruz, W. F. Crowley Jr., and P. A. Boepple Importance of Inhibin B in the Regulation of FSH Secretion in the Human Male J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5541 - 5546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ahn, S. You, H. Kim, Y. Chaiseha, and M. El Halawani Effects of Active Immunization with Inhibin {alpha} Subunit on Reproductive Characteristics of Turkey Hens Biol Reprod, November 1, 2001; 65(5): 1594 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.J. Tilbrook and I.J. Clarke Negative Feedback Regulation of the Secretion and Actions of Gonadotropin-Releasing Hormone in Males Biol Reprod, March 1, 2001; 64(3): 735 - 742. [Abstract] [Full Text]
|
|
|
|
|
|
A.J. Tilbrook, D.M. de Kretser, and I.J. Clarke Influence of the Degree of Stimulation of the Pituitary by Gonadotropin-Releasing Hormone on the Action of Inhibin and Testosterone to Suppress the Secretion of the Gonadotropins in Rams Biol Reprod, February 1, 2001; 64(2): 473 - 481. [Abstract] [Full Text]
|
|
|
|
|
|
S. Ramaswamy, G. R. Marshall, A. S. McNeilly, and T. M. Plant Dynamics of the Follicle-Stimulating Hormone (FSH)-Inhibin B Feedback Loop and Its Role in Regulating Spermatogenesis in the Adult Male Rhesus Monkey (Macaca mulatta) as Revealed by Unilateral Orchidectomy Endocrinology, January 1, 2000; 141(1): 18 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Winters and T. M. Plant Partial Characterization of Circulating Inhibin-B and Pro-{alpha}C During Development in the Male Rhesus Monkey Endocrinology, December 1, 1999; 140(12): 5497 - 5504. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
