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Biomedical subjects

C Desjardins

Publications and source records attributed to C Desjardins.

At least 37 records · Page 2Linked to original sources

Pulsatile release of luteinizing hormone and testosterone in male ferrets.

The temporal organization of LH and testosterone secretion was examined in male European ferrets. Hormone levels were measured in frequent blood samples taken via an indwelling jugular cannula from sexually mature and castrated ferrets. Intact ferrets discharge LH and testosterone in discrete pulses, but the frequency and amplitude of these pulses vary within and between individual males. The average frequency of LH pulses was 1.14 +/- 0.25 pulses/h, with an amplitude of 1.59 +/- 0.23 ng/ml in 11 ferrets. Testosterone pulse frequency and amplitude were 0.62 +/- 0.04 pulses/h and 16.96 +/- 2.5 ng/ml, respectively. The frequency, amplitude, and duration of hormone pulses were similar during the light and dark phases of the light-dark cycle. LH and testosterone peaks were temporally coupled with LH pulses preceding testosterone pulses by 10-20 min. However, not all LH pulses evoked a rise in testosterone. Frequently, trains of 2 or more LH pulses gave rise to a single testosterone pulse. Castration provoked a rapid increase in the frequency of LH pulses, and the interpulse interval became strikingly uniform within hours after orchidectomy. The amplitude of LH pulses, in contrast, increased gradually over the first 6 postcastration days and then plateaued at about 4.5 ng/ml. These findings demonstrate that LH pulses constitute functionally important signals to the testis, as evidenced by temporally related increments in testosterone secretion. Moreover, distinct differences in the development of the postcastration rise in the frequency and amplitude of LH pulses suggest that testosterone operates via multiple mechanisms to regulate LH release in the adult male. Finally, this study emphasizes the utility of the ferret as an animal model to study neural determinants of LH release in the male.

Animals↗

Differential effects of food restriction on pituitary-testicular function in mice.

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.

Animals↗

Spermatogenesis is modified by food intake in mice.

Spermatogenesis is generally viewed as being resistant to reduced food intake in inbred strains of adult mammals. This consensus stems from studies that have failed to place testicular responses within the context of a species' reproductive characteristics. We exposed two species of wild rodents, house mice and deer mice, to a mild but sustained food restriction (30% reduction of ad libitum consumption for 5 weeks). Reproductive adjustments made by each species to inanition were strikingly different. Food restriction failed to modify spermatogenesis in house mice, but evoked a continuum of testicular responses in deer mice ranging from normal spermatogenesis to azoospermia. These findings have several novel implications: 1) modest food restriction evokes species-specific adjustments in testicular function, and 2) intraspecific variation in spermatogenesis suggests robust individual differences in sensitivity to alterations in food intake. Taken together, our findings underscore the importance of considering the effects of food intake on male reproduction within the framework of a species' physiological and evolutionary background.

Animals↗

Orchidectomy unleashes pulsatile luteinizing hormone secretion in the rat.

We charted the development of pulsatile luteinizing hormone (LH) secretion as a function of the time elapsed after removal of the testes. On seven occasions between the moment of castration and 80 days afterwards, we obtained consecutive blood samples at frequent (2.5- to 5-min) intervals from cannulated male rats. Orchidectomy increased both the amplitude and frequency of LH release within 1 day after surgery. Amplitude: From 19 h through 80 days postcastration, peak LH levels rose steadily, and LH pulses grew progressively more pronounced in nadir-to-peak amplitude. Frequency: Our findings offer new evidence establishing an increase in LH pulse frequency from less than 1 per h to 2-3 per h within 1 day after orchidectomy. Once deprived of testicular influences, the frequency of pulsatile LH discharges remained static through 80 days. The sudden onset (less than 1 day after castration) and temporal uniformity of high-frequency LH pulses demonstrate that LH release is governed by an intrinsic, 20- to 30-min neural periodicity in castrate rats. Most important, these findings imply that the testes mask or modulate the expression of an intrinsic, 20- to 30-min neural generator directing the periodic discharge of LH in the intact male rat.

Animals↗

Mapping episodic fluctuations in plasma LH in orchidectomized rats.

Reports of the frequency of pulsatile LH release in orchidectomized rats are surprisingly variable. Estimates of the period between LH pulses vary from 18.5 to 250 min in nine reports from six laboratories, published in 1981-1983. In these studies, blood samples were drawn at intervals ranging from 2.5 to 60 min. We examined the relationship between estimated LH pulse frequency and blood-sampling interval. Six castrated male rats were cannulated, and blood samples were drawn at 2.5-min intervals through 4 h. Plasma LH levels were determined by radioimmunoassay. Using the data obtained at 2.5-min intervals, we simulated blood-sampling intervals of 5, 7.5, 10, 12.5, and 15 min by sequentially deleting data points. The original and simulated data sets were analyzed by both the PULSAR and Cycle Detector computer programs. The results show that as the sampling interval increased from 2.5 to 15 min, the apparent period of pulsatile LH release rose steadily from about 20 min to about 100 min. We found a high, positive correlation between blood-sampling interval and the apparent period of LH pulses. Estimates of LH pulse frequency in castrated male rats vary directly with the frequency at which blood samples are taken. Sampling intervals greater than 5 min in orchidectomized rats yield an LH pulse period that is most likely exaggerated.

Animals↗

Testicular function and sexual activity in senescent mice.

The steroidogenic potentials of testes from 6-mo-old and approximately 28-mo-old CB6F1 mice were compared by measuring the secretion rate of 11 steroids produced by testes perfused in vitro. Testes from 6- and 28- to 30-mo-old mice secreted similar amounts of testosterone, but marked differences in the secretion of testosterone biosynthetic intermediates were discovered. Testes of old mice produced significantly more (P less than 0.01) delta 5-steroids than young male mouse testes. The presence or absence of sexual activity among old male mice was not correlated with changes in testicular steroidogenesis or plasma steroid levels. The results suggest that selected alterations in androgen biosynthesis occur during aging, but that the decline in reproductive performance among old mice is not attributable to deficits in testicular steroidogenesis. Rather, age-associated losses in sexual activity may be mediated by disturbances in the central nervous system.

Aging↗

Development and characterization of a homologous radioimmunoassay for deer mouse (Peromyscus maniculatus bairdii) prolactin.

A highly specific and sensitive homologous radioimmunoassay has been developed for the secreted form of prolactin from the deer mouse Peromyscus maniculatus bairdii. Peromyscus serum and pituitary homogenates displayed parallel dilution response curves, and no cross reaction was seen with either mouse prolactin, mouse growth hormone or rat prolactin. The assay was sensitive to 25 picograms per tube and the intra- and inter-assay coefficients of variation were 5 and 3.6%, respectively. In addition, we have demonstrated that Peromyscus prolactin does not show parallel displacement in a homologous radioimmunoassay utilized for measuring prolactin in the common laboratory mouse.

Animals↗

In vitro perfusion of isolated mouse testes: a model system for investigating testicular steroidogenesis.

1. A procedure was developed to perfuse isolated mouse testes in vitro and investigate testosterone secretion. 2. The perfused testis preparation was validated by determining organ edema, glucose uptake, enzymatic and morphological indices of cellular integrity, and testosterone secretion in the absence and presence of LH and other pituitary peptides. 3. The results establish that this procedure can be exploited as a model system to investigate biochemical, physiological, and genetic aspects of steroidogenesis and Leydig cell function in the mouse, and presumably other small rodents as well.

Animals↗

Testis function in rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS;Silastic) implants for thirteen months. This steroid regimen inhibited LH but not FSH secretion by the anterior pituitary, inhibited testicular testosterone and estradiol production and drastically reduced the numbers of vigorously motile spermatozoa in the ejacula. Importantly, these effects on testis function were achieved at dosages of testosterone and estradiol which approximate the amount of these two steroids produced daily in normal rhesus males.

Animals↗

Somatic tissue responses of male rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS; Silastic) implants for thirteen months. This steroid regimen inhibited dramatically spermatogenesis. Gross and histopathological examination of the musculoskeletal, circulatory, endocrine (excluding the testis), central nervous, gastrointestinal and respiratory systems failed to uncover any untoward effects of the long-term exposure due to the contraceptive formulation. Similarly, no remarkable effects were observed in the ionic, chemical and formed elements of blood or secondary sex structures. Failure to detect secondary complications attributed to the steroid treatment offers further justification for evaluating a contraceptive strategy based on administering naturally occurring steroids at sustained rates approximating those at which they are produced endogenously in the human male.

Animals↗

Contraceptive efficacy of testosterone-estradiol implants in male rhesus monkeys.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS, Silastic) implants. This treatment caused a striking reversible sterility. No pregnancies were observed in females bred to the steroid-treated males. In contrast, there was no difference in pregnancy rate of females bred to control and steroid-treated monkeys for 14 weeks, beginning 17 weeks after removal of the steroid-filled implants.

Animals↗

Steroid secretion by mouse testes perfused in vitro.

We determined the concentration of steroids in blood plasma of CBF1 male mice and the steroidogenic potential of the mouse testis. Steroid secretion rates are based on measuring selected C18, C19, and C21 steroids in the venous effluent of testes perfused with a defined medium containing luteinizing hormone. Steroids were isolated by thin-layer and/or column chromatography and quantified by radioimmunoassay. These include pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, 3 alpha-androstanediol, and 3 beta-androstanediol. Testosterone is the primary steroid secreted by mouse testes perfused in vitro and is the chief androgen present in blood plasma. Pregnenolone, an obligatory intermediate in steroid synthesis, is converted to testosterone via two separate steroidogenic pathways in approximately equal proportions. This is unlike other species in which testosterone biosynthesis proceeds preferentially via either the delta 4 or the delta 5 pathway. Our results, taken together, provide the first comprehensive assessment of Leydig cell steroidogenic activity in the mouse, demonstrate putative enzymatic pathways subserving androgen biosynthesis, and establish the predominant steroids in the peripheral circulation of adult mice.

Androgens↗

Control of pulsatile LH release in male rats.

Distinct, short-term pulses of pituitary luteinizing hormone (LH) release are a characteristic feature of tonic LH secretion in normal rats. LH pulses are more pronounced, more frequent, and more regular in castrated rats. Using castrated rats, we sought to identify the basis of the pulsatile discharge of LH by the pituitary gland. Indwelling atrial cannulae were used to obtain frequent blood samples through 3-4 h from three cohorts of conscious, freely moving, orchidectomized male rats. Rats were (1) untreated castrates, (2) infused with ovine antiserum to LHRH or control serum, or (3) infused with a luteinizing hormone releasing hormone (LH-RH) analog, [D-pGlu1,D-Phe2, D-Trp3,6]-LH-RH. Castrates exhibited a pulsatile pattern of circulating LH levels; the mean (+/- SE) peak level of LH pulses was 640 +/- 15 ng/ml, with a mean (+/- SE) pulse period of 18.5 +/- 0.8 min. LH-RH antiserum arrested pulsatile LH secretion immediately, leaving plasma LH levels at 80-120 ng/ml. The LH-RH analog caused a similar suppression of LH release, although this effect was of a shorter duration than the suppression of LH pulses induced by LH-RH antiserum. The obliteration of LH pulses by anti-LH-RH and suppression of LH release by an LH-RH antagonist indicate that the pulsatile secretion of LH is due to corresponding stimulation of the pituitary gland by hypothalamic LH-RH. Anti-LH-RH and an LH-RH antagonist are identified as valuable probes for the experimental dissection of blood-borne signals within the rat hypothalamic-pituitary-testicular axis.

Animals↗

Vasculature of the mouse, rat, and rabbit testis-epididymis.

The arrangement of blood vessels serving the testis-epididymis vas investigated microscopically in the mouse, rat, and rabbit. Blood vessels were visualized by infusing liquid silicone rubber into the vessels and subsequently clearing the surrounding tissue. Comprehensive illustrations of the vasculature were prepared from three-dimensional examinations. Arterial and venous vessels serving the testis-epididymis follow similar routes in all three species. However, the arrangements and characteristics of the blood vessels demonstrate dramatic species differences. For example, arteries within the testes have tight coils in the mouse and artery-artery anastomoses in the rat. Veins form vascular pathways that connect the testis and efferent ductules in all three species but also form a connection between the testis and cauda epididymidis in the rabbit only. Testosterone concentrations were determined in blood obtained by micropuncture of selected testis-epididymal veins. The measurements establish that the highest levels of testosterone are found in testicular surface veins. Also, vas deferential veins of the rabbit had significant amounts of testosterone. Studies of the blood-vessel volumes suggested that the volumes of arteries and veins in the testis are similar, whereas venous volumes exceed arterial volumes in all of the other organs examined. The studies provide comprehensive information about the architecture and physiology of blood vessels serving the testis-epididymis in the mouse, rat, and rabbit. Each species exhibits diversity in the vasculature and testosterone content of the veins. Veins connecting the testis to the efferent ductules and cauda epididymidis may provide for the preferential delivery of testicular secretions to androgen-dependent organs before the secretions are metabolized or diluted in the systemic blood.

Animals↗