| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular article |
a Departments of Cell Biology and Physiology and
b Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
ABSTRACT
In this study, we determined the relative role of LH and FSH in initiating the pubertal proliferation of Sertoli cells in primates. Sixteen juvenile male rhesus monkeys (Macaca mulatta) bearing venous catheters received intermittent intravenous infusions of single chain human LH (schLH) or recombinant human FSH (rhFSH) or a combination of both for 11 days. The schLH infusion elicited a physiological testosterone response. On Day 11, monkeys were castrated, and one-half of a testis was fixed in Bouin's fluid. Infusion of the gonadotropins, either alone or in combination, effected a significant increase in testicular weight, seminiferous cord diameter, and the number of Sertoli cells per testis (schLH, 295 ± 46 x 106; rhFSH, 342 ± 64 x 106; LH+FSH, 298 ± 26 x 106 versus vehicle, 204 ± 26 x 106). The latter finding indicated that LH, in addition to FSH, plays a critical role in the initiation of the pubertal proliferation of Sertoli cells in primates. Moreover, combined gonadotropin treatment led to the appearance of germ cells as mature as early primary spermatocytes, indicating that initiation of spermatogenesis had been set in motion. Because the duration of hormone stimulation was only 11 days, the latter result suggests that Leydig and Sertoli cells of the juvenile monkey testis can immediately transduce a gonadotropin signal to the germ cell.
FSH, LH, puberty, Sertoli cells, spermatogenesis
INTRODUCTION
In humans and rhesus monkeys (Macaca mulatta), a marked proliferation of Sertoli cells occurs at puberty [1, 2] and, in the monkey, this proliferation may be induced precociously by activating pituitary gonadotropin secretion in the juvenile with pulsatile GnRH stimulation [2]. A limited number of studies have sought to address the issue of the relative role of FSH and LH in driving Sertoli cell proliferation at the time of primate puberty [3, 4]. In one study, administration of either purified human FSH (hFSH) or testosterone (T) to juvenile monkeys over a period of 12 wk resulted in an increase in the number of Sertoli cells per cross section [3]. In another study, however, injections of either hFSH or hCG over 4 wk failed to result in a significant increase in the number of Sertoli cells per testis [4]. Thus, a definitive conclusion regarding the relative role of FSH and LH in regulating the pubertal proliferation of primate Sertoli cells is lacking. In rodents, however, it is generally recognized that FSH is the major regulator of Sertoli cell proliferation [5–8].
To further examine the relative importance of FSH and LH in stimulating Sertoli cell proliferation at the time of puberty in primates, juvenile rhesus monkeys were treated with recombinant single chain human LH (schLH) and recombinant hFSH (rhFSH), either alone or in combination, for 11 days. The recombinant gonadotropins were delivered in an intermittent fashion as a brief intravenous infusion once every 3 h, the approximate pulse frequency of endogenous gonadotropin secretion in adult males [9]. The results of the present study provide unequivocal evidence that in the rhesus monkey, both LH and FSH are able to initiate a precocious pubertal proliferation of Sertoli cells.
MATERIALS AND METHODS
Animals
Sixteen juvenile male rhesus monkeys (16–19 mo of age, 2.2–3.7 kg body weight [BW]) were used. In this species, the onset of puberty, as reflected by the initiation of nocturnal T secretion, occurs at approximately 30 mo of age [10]. The animals were maintained under a controlled photoperiod (lights-on 0700–1900 h) in accordance with the NIH Guidelines for the Care and Use of Laboratory Animals, and the experimental procedures were approved by the Institutional Animal Use and Care Committee.
Access to Venous Circulation
Each monkey was implanted with two venous catheters and housed in remote sampling cages for the infusion of recombinant gonadotropins and for the collection of sequential blood samples without tranquilization and with minimal restraint, as described previously [11]. Postsurgically, the animals received a single intramuscular injection of penicillin (300 000 U; Bicillin L-A, Wyeth Laboratories, Philadelphia, PA) and intravenous injections of a broad spectrum antibiotic (100 mg cefazolin sodium; Kefzol, Apothecon, Princeton, NJ), and an analgesic (1 mg/kg BW meperidine hydrochloride; Demerol, Elkins-Sinn, Cherry Hill, NJ) twice daily for 4 days. The monkeys were allowed to adapt to the infusion and withdrawal system for a minimum of 1 wk before the initiation of the gonadotropin treatments.
Blood samples (1–3 ml) were drawn in heparinized syringes and collected in sterile tubes. During frequent blood sampling, 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.
Hormone Infusates
Both schLH and rhFSH, the characteristics of which have been described previously [12, 13], were provided by the National Hormone and Pituitary Program (Torrance, CA). A stock solution of each of the recombinant gonadotropins (schLH, 300 IU/ml; rhFSH, 200 IU/ml) was prepared by diluting the lyophilized hormone with sterile Dulbecco's PBS (DPBS without CaCl2 and MgSO4; Gibco BRL Products, Grand Island, NY). Custom infusates were prepared individually for each animal as follows. On the day before initiating the hormone treatment, a working solution for each hormone (schLH, 3.3–4.8 IU/ml; rhFSH, 2.2–2.9 IU/ml) was made by diluting the stock solution with DPBS. The infusates also contained cefazolin sodium (1 µg/ml) and the appropriate monkey serum (1%), which had been collected before initiation of the experiment. DPBS containing cefazolin sodium, and the appropriate monkey serum constituted vehicle infusate. The infusates were stored frozen in fractions of 30 ml at -20°C. Fractions of infusates were thawed overnight at 4°C, as required, to replenish the infusion reservoir.
Experimental Design
Groups of four monkeys each received intermittent intravenous infusions (2 ml for 1 min, every 3 h) of either schLH (3 IU/kg) or rhFSH (2 IU/kg), of a combination of schLH and rhFSH (3 and 2 IU/kg, respectively), or of vehicle. The mean (±SD) age of monkeys in the foregoing groups was 16.8 ± 0.5 mo, 17.2 ± 1.5 mo, 17.8 ± 0.8 mo, and 17.0 ± 1.4 mo, respectively. One of the remote sampling lines was dedicated to gonadotropin administration, and the other was used for blood sampling. (In one of the monkeys receiving rhFSH infusion, the patency of one catheter was lost on Day 1 of infusion. In this monkey, therefore, the remaining line was used for both infusion and blood sampling. For the purpose of calculating the mean concentration of circulating hFSH, however, values from this monkey were excluded.) Prior to the initiation of the infusions on Day 0, the dead space in the infusion line was first filled with the appropriate infusate before the initiation of pulsatile delivery using a peristaltic pump (Gilson Minipuls-3; Gilson Medical and Electrical Co., Middletown, WI) controlled by a programmable timer (Chrontrol, Chrontrol Corp., San Diego, CA). A single blood sample was taken prior to initiation of the gonadotropin infusions at 0900 h on Day 0. The profiles of the circulating concentrations of the recombinant hormones resulting from the intermittent infusions were determined in frequent blood samples collected during selected 3-h interpulse intervals on Days 1 (9th pulse), 8 (65th pulse), and 11 (88th pulse) of the experiment. These samples also served to describe the testicular T response to stimulation with the gonadotropins.
Testicular dimensions (length l and breadth w of each testis) were recorded before treatments began and on Days 4 and 7 following initiation of hormone infusions. These dimensions were used to calculate testicular volume (v) using the formula v = (
lw2) ÷ 6. On Day 11, intermittent gonadotropin stimulation was terminated after the monkeys received the 0900 h infusion, and bilateral castration was performed between 1200 and 1300 h on the same day. The 11-day course of gonadotropin stimulation was selected after an increase in testicular volume was detected in the first two animals following 4 days of hormone treatment. The testes were weighed individually, and for the purpose of the present study, one-half of a testis chosen randomly was fixed in Bouin's fixative and processed to determine the number of Sertoli and germ cells.
Morphometry
All morphometric data were generated using the stereological method described previously [2]. Ten sections, 4 µm thick, were cut from a paraffin block and stained with periodic acid-Schiff-hematoxylin. The volume fractions (Vv) of the seminiferous cords were determined in each monkey by examining 4000 test points on a randomly selected section [14, 15]. The diameter (Ds) of 15 cross sections of seminiferous cord per monkey were measured with a calibrated ocular micrometer.
The number of cells (Ns) in cross sections of seminiferous cords (150–200 cells/testis) defined by circular profiles were counted, and the cell counts were corrected by the method of Abercrombie [16]. The numbers of Sertoli cells and Ad and Ap spermatogonia per testis were estimated from the product of total length of the seminiferous compartment (L) and Ns of each cell type. The seminiferous cords were assumed to be cylindrical and their lengths were estimated from absolute volume (Vs) and Ds [17]. The numbers of Sertoli, Ad, and Ap cells were then multiplied by total cord length to yield the number of each cell type per testis. The numbers of other germ cell types, however, were expressed per cross section.
Assays
Gonadotropins Circulating profiles of schLH and rhFSH were measured using assay kits specific for hLH and hFSH (Technicon Immuno-1 System; Bayer Corporation, Diagnostic Division, Tarrytown, NY), respectively. The standard for the hFSH heterogeneous sandwich magnetic separation immunoassay was calibrated against the World Health Organization (WHO) 2nd International Reference Standard, 78/549. The sensitivity of this assay was 0.1 IU/L, and both intra- and interassay coefficients of variation were <5%. The hLH assay was also a heterogeneous sandwich magnetic separation immunoassay with the standard calibrated against the WHO 1st International Reference Standard for pituitary LH, IRP 68/40. The sensitivity of the assay was 0.3 IU/L, and both intra- and interassay coefficients of variation were <7%. For calculation of the mean concentrations of hLH and hFSH, hormone levels below the sensitivity of the assay were assigned a value equivalent to the minimum detectable concentration in the respective assays.
Testosterone Plasma T was assayed in duplicate by a previously described RIA [18] employing antiserum T3-125 (Endocrine Sciences, Tarzana, CA). The mean sensitivity of the assay was approximately 0.05 ng/ml, and the intra- and interassay coefficients of variation were 6.0% and 10.8%, respectively.
Statistical Analyses
The significance of differences among the four groups was determined using an ANOVA and, where appropriate, followed by the Newman-Keuls test [19]. The significance of differences in testicular volume was determined using a two-way ANOVA followed by the Newman-Keuls test [19]. A difference generating a value of P < 0.05 was considered to be significant, and the data are expressed as mean ± SD.
RESULTS
Circulating Profiles of Hormones
Prior to the initiation of recombinant hormone infusions and during vehicle infusion, concentrations of hLH and hFSH in the circulation of juvenile monkeys were undetectable. Intermittent infusion of schLH or rhFSH resulted in an episodic pattern in the circulating concentrations of hLH and hFSH, respectively (Fig. 1). Combined administration of the recombinant hormones did not influence their pulsatile profiles (data not shown). By Day 8 of intermittent stimulation with schLH, the pattern of testicular T secretion was pulsatile, with circulating concentration of this steroid reaching a peak of approximately 4 ng/ml (Fig. 1). A quantitatively similar pulsatile pattern of T secretion was also observed following combined administration of the recombinant gonadotropins (data not shown). However, intermittent stimulation with rhFSH alone did not elicit an episode of T secretion (Fig. 1).
|
Testicular Volume and Weight
The mean combined volume of the testes prior to the initiation of vehicle or hormone infusions was approximately 0.35 ml. A significant increase in this parameter was noted in monkeys treated with the recombinant gonadotropins, either alone or in combination, as early as Day 4 of hormone infusions (0.62 ± 0.24 ml, 0.61 ± 0.03 ml, and 0.65 ± 0.04 ml, in schLH-treated, rhFSH-treated, and combined schLH plus rhFSH-treated groups, respectively). By Day 7, a further increase in the mean combined volume of testes was evident in the schLH (0.70 ± 0.3 ml) and combined gonadotropin (0.82 ± 0.07 ml) groups but not in the rhFSH (0.60 ± 0.05 ml) group. The Day 7 values for testicular volume were significantly greater than those for vehicle and for Day 0 in all treatment groups. The changes in mean combined testes volume in vehicle-treated monkeys were unremarkable.
At the end of 11 days of vehicle infusion, the mean combined weight of testes in this group was 0.56 ± 0.14 g (Table 1). As shown in Table 1, a significant increase in the combined weight of testes was noted in monkeys treated with schLH (1.05 ± 0.15 g), rhFSH (0.91 ± 0.12 g), or a combination of the two (1.14 ± 0.11 g). Moreover, the combined weight of testes in monkeys treated with schLH, either alone or in combination with rhFSH, was also significantly greater than that of the group treated with rhFSH alone.
|
Histology and Morphometry
Seminiferous cords surrounded by dense fibrous tissue and containing numerous immature Sertoli cells, with ellipsoid nuclei, and stem (Ad and Ap) spermatogonia was a common feature of the testicular parenchyma of all groups (Fig. 2, A–D). Germ cells more mature than stem spermatogonia were noted only in those monkeys treated with rhFSH, either alone or in combination with schLH (Fig. 2, C and D). The mean diameter of the seminiferous cords was significantly greater in the testes of monkeys treated with recombinant gonadotropins, either alone or in combination, than in those in vehicle-treated group (Table 1). Differences in the length of the seminiferous cord among the four groups were not observed (Table 1).
|
The mean number of Sertoli cells per testis was significantly greater in the schLH-treated group than in the vehicle-treated group (Fig. 3). Sertoli cell number was also significantly increased by treatment with rhFSH, either alone or in combination with schLH (Fig. 3). No difference was observed in the number of this cell type per testis among the three hormone-treated groups. The morphology of Sertoli cell nuclei was indistinguishable at the end of the experiment among all four groups.
|
The mean number of Ad spermatogonia per testis in the vehicle (14.4 ± 3.8 x 106) and schLH (18.0 ± 6.4 x 106) groups was indistinguishable. However, a significant reduction in the mean number of this stem cell type was noted in monkeys treated with rhFSH either alone (9.4 ± 1.3 x 106) or in combination with schLH (7.0 ± 1.8 x 106). Moreover, the mean number of Ad spermatogonia in the latter group was also significantly different from that in monkeys treated with schLH alone. In contrast, differences were not observed in the number of Ap spermatogonia per testis (11.8 ± 0.6 x 106, 9.4 ± 3.7 x 106, 13.4 ± 3.1 x 106, and 9.8 ± 0.8 x 106, in vehicle, schLH, rhFSH, and combined schLH and rhFSH groups, respectively).
Although germ cells more mature than undifferentiated spermatogonia were not apparent in the testes of monkeys treated with vehicle or schLH, a few differentiated type B1 spermatogonia (1.3 ± 1 cell/cross section) were observed in three of the four monkeys treated with rhFSH. This cell type was present in only 1.3–3% of the total cross sections of seminiferous cords observed. However, the testes of monkeys receiving combined rhFSH and schLH treatment showed the presence of all four generations of differentiated spermatogonia (B1, B2, B3, B4) and preleptotene and leptotene-zygotene spermatocytes (Fig. 4). In this group, between 26% and 38% of the total cross sections of seminiferous cords observed contained at least one differentiated spermatogonium and/or spermatocyte.
|
DISCUSSION
The episodic testicular T response to intermittent stimulation with schLH on Day 8 of treatment was reminiscent of the high-fidelity relationship that exists between endogenous LH discharges and T secretion in adult monkeys [9]. Thus, we concluded that the intermittent infusion of schLH employed in the present study provided the Leydig cells of the juvenile testes with a physiological stimulus. However, the intermittent infusion of rhFSH is more difficult to place into perspective because a precise endocrine marker of bioactivity for this gonadotropin is not available. However, the circulating immunoactive levels of hFSH achieved in the juvenile monkey by infusion of the recombinant hormone were only marginally greater than those of endogenous FSH in the circulation of normal men [20]. It would therefore seem that the rhFSH infusion provided a reasonable physiological stimulus to the juvenile testes.
The present finding that a significant increase in testicular volume occurred as early as Day 4 of treatment with the recombinant gonadotropins, either alone or in combination, is consistent with the previously reported rapid testicular growth in response to gonadotropin treatment in juvenile monkeys [21]. Thus, the Sertoli and Leydig cells of the juvenile primate testis must express functional FSH and LH receptors that are coupled to appropriate signal transduction pathways.
The major cellular component of the juvenile monkey testis is the Sertoli cell [2], and proliferation of this somatic cell type was primarily responsible for the increase in testicular size observed in response to the gonadotropin treatments in the present study. The finding that schLH and rhFSH alone were equally as effective in increasing Sertoli cell number in the juvenile testis unequivocally demonstrates that initiation of the pubertal proliferation of this somatic cell type may be elicited by a selective increase in LH stimulation. This finding would appear to be in contrast to the situation in rodents. In normal or gonadotropin-deficient mice, administration of hCG during the neonatal period of development did not enhance Sertoli cell proliferation [8, 22]. Although the finding that mice lacking FSHß or FSH receptors are fertile [23, 24] may be taken to infer that LH may stimulate postnatal Sertoli cell proliferation, Sertoli cell number was not determined in these studies. However, FSH administration to normal rodents and gonadotropin-deficient mice at this stage of development increases Sertoli cell number [8, 22, 25, 26], and it is generally recognized that this gonadotropin is the major stimulus for postnatal Sertoli cell proliferation in rodents [7].
Because premature imposition of a selective increase in circulating concentrations of either LH or FSH in the juvenile monkey can initiate a precocious pubertal proliferation of Sertoli cells, it seems reasonable to propose that the gonadotropin milieu that provides the physiological stimulus for this developmental event will be determined by the temporal relationship between the time courses of circulating LH and FSH concentrations during the peripubertal period. In the monkey, data describing pubertal changes in gonadotropin secretion are fragmentary, but in an extensive literature exists on this subject for humans. Although it was originally considered that in boys an increase in FSH secretion preceded that of LH at the time of puberty [27], more sensitive assays suggest that the pubertal activation of LH and FSH release occurs concomitantly [27–29]. Thus, in primates both LH and FSH appear to contribute to the quantitatively important phase of Sertoli cell proliferation at the time of puberty.
That stimulation of Sertoli cell number by LH is mediated by T secreted from the Leydig cell, is consistent with the finding that treatment of juvenile monkeys with this androgen resulted in an increase in the number of Sertoli cells per cross section [3]. This putative paracrine action of T on the Sertoli cell is probably mediated by the androgen receptor [30], whereas the action of FSH most likely involves activation of the cAMP-protein kinase A-cAMP response element binding protein (CREB) pathway [31]. Thus, activation of either of these two signal transduction pathways causes the Sertoli cell to proceed through the cell cycle. Moreover, the absence of an additive action of LH (T) and FSH stimulation on Sertoli cell division suggests that both pathways ultimately interact with the same checkpoints of the cell cycle [32].
The present study also provided an opportunity to examine the immediate effects of gonadotropin treatment, either alone or in combination, on the early steps in the initiation of spermatogenesis in the monkey. In this regard, the most striking result was obtained with combined gonadotropin treatment. Considering that in the monkey maturation of undifferentiated spermatogonia to leptotene-zygotene spermatocytes requires the duration cycle of the seminiferous epithelium, which in these species is 10.5 days [33], the appearance of these primary spermatocytes in some segments of the seminiferous cord during the 11 days of combined gonadotropin stimulation indicates that the activation of this process must have occurred immediately. This inference reinforces the idea that somatic cells of the juvenile testis are able to immediately respond to appropriate gonadotropin stimulation and extends this notion to germ cells. Specifically, certain cohorts of Ap spermatogonia and their progeny must be able to respond to the signals relayed by the Sertoli and Leydig cells in response to the gonadotropin drive.
In monkeys treated with rhFSH alone, only a few differentiated (B1) spermatogonia were present in the seminiferous cords, and schLH treatment did not appear to affect germ cells. In contrast to the situation for Sertoli cell proliferation, the presence of an additive action of LH and FSH stimulation on germ cell division suggests that T and FSH elicit different responses from the Sertoli cell that together contribute to the immediate maturation of germ cells observed with combined treatment.
The failure of LH stimulation to activate the first steps in the initiation of the spermatogenic process is perhaps not surprising because chronic exogenous T administration to juvenile monkeys is required to initiate qualitatively normal spermatogenesis [34].
Because premature stimulation of the juvenile testes achieved by elevating endogenous gonadotropins with pulsatile GnRH treatment for 10 wk [2] was correlated with an increase in Ap spermatogonia number, we anticipated a similar change in undifferentiated spermatogonia in association with the appearance of primary spermatocytes during combined gonadotropin treatment. This result, however, was not observed. The irregular and limited distribution of differentiated spermatogonia and spermatocytes in the testes of the animals receiving combined gonadotropin treatment suggests that the number of Ap spermatogonia dividing at any moment must be small. Thus, the expected increase in Ap spermatogonia may have escaped detection.
A significant decrease in Ad spermatogonia was noted in the present study in monkeys treated with either rhFSH alone or rhFSH in combination with schLH but not in those treated with schLH alone. This situation is in contrast to the results of earlier studies involving longer exposure of the immature monkey testes to gonadotropins [2, 4]. A significant decrease in Ad spermatogonia was also noted in a recent study in which an increase in endogenous FSH secretion was elicited by unilateral orchidectomy in adult monkeys [35]. We have no explanation for these observations that is consistent with the current understanding of the role of this stem cell in the spermatogenic process [36].
In summary, the findings of the present study indicate that LH stimulation alone can initiate the pubertal proliferation of Sertoli cells in primates and that the Leydig cell and Sertoli cell of the juvenile monkey testis are able to immediately transduce a gonadotropin signal to the germ cell.
ACKNOWLEDGMENTS
The expert technical assistance of Deborah A. Bolette, Michael A. Cicco, and the staff of the Primate and Assay Cores of the Center for Research in Reproductive Physiology, University of Pittsburgh School of Medicine, is gratefully acknowledged. The recombinant hormones used in this study were obtained from the National Hormone and Pituitary Program (NIH contract HD92922).
FOOTNOTES
First decision: 11 January 2000.
1 A preliminary report of this work, which was supported by NIH grants HD 32473, HD 08610, and HD13254, was presented at the 32nd Annual Meeting of the Society for the Study of Reproduction, July 1999, Pullman, WA. 
2 Correspondence: Gary R. Marshall, Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, E1140 Biomedical Science Tower, 200 Lothrop St., Pittsburgh, PA 15261-2582. FAX: 412 648 3290; marshg+{at}pitt.edu
Accepted: February 15, 2000.
Received: December 13, 1999.
REFERENCES
This article has been cited by other articles:
|
|
 |
|
  R. Rathi, W. Zeng, S. Megee, A. Conley, S. Meyers, and I. Dobrinski Maturation of Testicular Tissue from Infant Monkeys after Xenografting into Mice Endocrinology, October 1, 2008; 149(10): 5288 - 5296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Scott, G. R. Hutchison, M. S. Jobling, C. McKinnell, A. J. Drake, and R. M. Sharpe Relationship between Androgen Action in the "Male Programming Window," Fetal Sertoli Cell Number, and Adult Testis Size in the Rat Endocrinology, October 1, 2008; 149(10): 5280 - 5287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Scott, G. R. Hutchison, I. K. Mahood, N. Hallmark, M. Welsh, K. De Gendt, G. Verhoeven, P. O'Shaughnessy, and R. M. Sharpe Role of Androgens in Fetal Testis Development and Dysgenesis Endocrinology, May 1, 2007; 148(5): 2027 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Raivio, A. M Wikstrom, and L. Dunkel Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome Eur. J. Endocrinol., January 1, 2007; 156(1): 105 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rasheed, X. Wang, Q.-T. Niu, J. Yeh, and B. Li Atm-deficient mice: an osteoporosis model with defective osteoblast differentiation and increased osteoclastogenesis Hum. Mol. Genet., June 15, 2006; 15(12): 1938 - 1948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Kumar, N. Pitteloud, P. A.M. Andrews, A. Dwyer, F. Hayes, W. F. Crowley Jr, and M. Dym Testis morphology in patients with idiopathic hypogonadotropic hypogonadism Hum. Reprod., April 1, 2006; 21(4): 1033 - 1040. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
K. A. L. Tan, K. De Gendt, N. Atanassova, M. Walker, R. M. Sharpe, P. T. K. Saunders, E. Denolet, and G. Verhoeven The Role of Androgens in Sertoli Cell Proliferation and Functional Maturation: Studies in Mice with Total or Sertoli Cell-Selective Ablation of the Androgen Receptor Endocrinology, June 1, 2005; 146(6): 2674 - 2683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N Atanassova, M. Walker, C. McKinnell, J. S Fisher, and R. M Sharpe Evidence that androgens and oestrogens, as well as follicle-stimulating hormone, can alter Sertoli cell number in the neonatal rat J. Endocrinol., January 1, 2005; 184(1): 107 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Simorangkir, S. Ramaswamy, G. R. Marshall, and T. M. Plant In the Adult Male Rhesus Monkey (Macaca mulatta), Unilateral Orchidectomy in the Face of Unchanging Gonadotropin Stimulation Results in Partial Compensation of Testosterone Secretion by the Remaining Testis Endocrinology, November 1, 2004; 145(11): 5115 - 5120. [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]
|
|
|
|
|
|
A. Honaramooz, M.-W. Li, M. C. T. Penedo, S. Meyers, and I. Dobrinski Accelerated Maturation of Primate Testis by Xenografting into Mice Biol Reprod, May 1, 2004; 70(5): 1500 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Walker Molecular Mechanisms Controlling Sertoli Cell Proliferation and Differentiation Endocrinology, September 1, 2003; 144(9): 3719 - 3721. [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]
|
|
|
|
 |
|
 R.I. McLachlan, L. O'Donnell, S.J. Meachem, P.G. Stanton, D.M. de Kretser, K. Pratis, and D.M. Robertson Identification of Specific Sites of Hormonal Regulation in Spermatogenesis in Rats, Monkeys, and Man Recent Prog. Horm. Res., January 1, 2002; 57(1): 149 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
L. O’Donnell, A. Narula, G. Balourdos, Y.-Q. Gu, N. G. Wreford, D. M. Robertson, W. J. Bremner, and R. I. McLachlan Impairment of Spermatogonial Development and Spermiation after Testosterone-Induced Gonadotropin Suppression in Adult Monkeys (Macaca fascicularis) J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1814 - 1822. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) in the circulation in response to the episodic schLH stimulation of the testes of the juvenile hypogonadotropic monkey resemble those normally seen in the adult monkey [
