Biomedical subjects

S D Michael

Publications and source records attributed to S D Michael.

At least 19 recordsLinked to original sources

PubMed1998

The application of volume deformation to three-dimensional facial reconstruction: a comparison with previous techniques.

Facial reconstruction has been widely criticised for its subjective nature and is thus often viewed as a last resort. Recent computer-aided reconstructions, which claim to be objective, may be subject to similar errors. To date, both manual reconstructions and computer-aided techniques have been limited to using the same tissue depth data reference tables. We propose that it is not solely the accuracy of the soft tissue depth data, but the sparsity of landmarks, which contributes to a lack of understanding of how soft tissue changes between the landmarks. The authors feel that a new approach to facial reconstruction using a computer graphics technique known as volume deformation addresses some of the problems encountered in the past. A review of previous methods is provided with discussion of the strengths and limitations of these techniques. In addition, areas are highlighted where the new deformation-based approach may offer possible solutions.

Computer Graphics↗

PubMed1998

Analysis of steroid hormone levels in female mice at high population density.

Populations of predominantly female house mice (Mus musculus) were created by placing virgin female mice in cages (0.045 m2 to 0.48 m2) with a single stud male, and removing all ensuing male offspring at weaning. At maximum population size, the females in these all-female/one-male populations exhibited male-like aggressive behavior. Termination of the populations and subsequent measurement of steroid hormone levels indicated that the aggressive females had high circulating level of testosterone and corticosterone, and elevated baseline levels of progesterone. The high levels of corticosterone could be lowered by dexamethasone, but not the high levels of testosterone.

Aggression↗

PubMed1997

Estradiol down-regulates LPS-induced cytokine production and NFkB activation in murine macrophages.

PROBLEM: In vivo and in vitro studies have indicated that estradiol can affect cytokine production in different cell types. This study examines whether estradiol affects inflammatory cytokine production by murine splenic macrophages. METHODS: Mouse splenic macrophages were first treated with 17 beta-estradiol, followed by lipopolysaccharide (LPS) stimulation. The production of cytokines by macrophages with or without estradiol treatment was determined at both the protein and mRNA levels. The nuclear factor-kB (NFkB) activity of activated mouse splenic macrophages was also evaluated by electrophoretic mobility shift assay. RESULT: Our results show that 17 beta-estradiol decreases LPS-induced IL-1 alpha, IL-6, and TNF-alpha production but not IL-10, IL-12, and macrophage inflammatory protein (MIP) production by splenic macrophages. Furthermore, inhibition of cytokine production by 17 beta-estradiol was associated with a decreased LPS-induced NFkB-binding activity. CONCLUSION: Because cytokines are important mediators of immune function, the alteration of cytokine production by 17 beta-estradiol may thus have a profound effect on the outcome of immune response during inflammation.

Animals↗

PubMed1997

The anovulation in female mice resulting from postnatal injections of estrogen is correlated with altered levels of CD8+ lymphocytes.

PROBLEM: Injections of estradiol-17 beta (E2) are known to both induce anovulation and alter lymphocyte maturation in female mice. The current study examined whether the two events are related. METHOD OF STUDY: Female (C3H/HeJ x 129J)F1 (C31) mice were injected with 20 micrograms of E2 from 0-3 days, or from 3-6 days, postpartum. At 8, 12, 20, 32, or 40 weeks of age, the animals were killed, T lymphocytes were characterized, and ovaries were histologically examined for the presence of corpora lutea. RESULTS: Animals injected with E2 from 0-3 days postpartum had percentages of CD8+ thymocytes and CD8+ splenocytes that were always lower than in noninjected females, and the E2-injected animals never ovulated, even by 40 weeks of age. In contrast, animals injected with E2 from 3-6 days of age had percentages of CD8+ thymocytes and CD8+ splenocytes that, although initially lower than in control females, attained control values by 32 weeks of age. In addition, at 32 weeks of age a number of the 3-6-day E2-injected females ovulated, whereas at earlier ages none had. Further, injections of E2 had little effect on the percentages of CD4+ thymocytes and splenocytes in these animals. CONCLUSIONS: The results suggest that E2-induced anovulation in C31 female mice is correlated with decreased levels of CD8+ lymphocytes, and an increased CD4+/CD8+ lymphocyte ratio.

Animals↗

PubMed1996

Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3.

In genetically susceptible strains of mice, such as A/J and (C57BL/6J x A/J)F1 hybrids, neonatal thymectomy-induced autoimmune ovarian dysgenesis (AOD) is characterized by the development of antiovarian autoantibodies, oophoritis, and atrophy. Temporally, atrophy may be observed during and after the regression of inflammatory infiltrates from the ovary. Histologically, lesions appear as areas devoid of ovarian follicles in all stages of development that have been replaced by luteinized interstitial cells. We report here the mapping of Aod2, the locus that controls this phenotype, to mouse chromosomes 3 within a region encoding Il2 and Fgfb. Most significant, however, is the co-localization of Aod2 to Idd3, a susceptibility gene that plays a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse.

Animals↗

PubMed1996

Quantitative changes in macrophage distribution in normal mouse ovary over the course of the estrous cycle examined with an image analysis system.

PROBLEM: The current study considered the distribution of macrophages within the major ovarian structures throughout the estrous cycle. METHODS: Immunohistochemical analyses were carried out using an avidin-biotin-peroxidase staining method and the rat anti-mouse macrophage monoclonal antibody anti-Mac-l was applied to stain macrophages. A computer-assisted image analysis system was used to quantify and compare the distribution of macrophages within individual ovarian structures during the estrous cycle. The following morphological structures were analyzed: primordial, preantral, antral, pre-Graafian, and atretic follicles; first-, second-, and third-generation corpora lutea; and the interstitium. The analysis included follicular and corpus luteum substructures: theca, granulosa cells, and interstitium. The system allows the estimation of macrophage distribution as a macrophage density per microns2 of the defined area. RESULTS: Primordial and preantral follicles did not contain macrophages during all stages of the estrous cycle. In antral, pre-graafian, and graafian follicles, macrophages were located and quantified only in the theca and were not detected in the granulosa cell layer. In contrast, atretic follicles showed macrophage localization in both thecal and granulosa cell layers. Macrophages were present in small numbers in the granulosa luteal cell layer and in high numbers in the thecal layer of newly developing corpora lutea. In the second generation of corpus luteum, macrophages followed the same pattern of distribution, while old corpora lutea contained significantly higher numbers of macrophages in both thecal and luteal cell layers. Surprisingly, significant quantitative changes in the macrophages distribution were detected over the course of the estrous cycle. Macrophage density was significantly higher in proestrus and metestrus when compared with the density in diestrus and estrus in most of the studied substructures with the exception of atretic follicles. Atretic follicles showed high macrophage density throughout the cycle with a two-fold higher density at metestrus. CONCLUSION: Macrophages were present in the mouse ovary over the course of the estrous cycle. The greatest numbers of macrophages appearing in corpora lutea and in atretic follicles suggest a role for macrophages in corpus luteum differentiation and follicular atresia. Their patterns of distribution at proestrus and metestrus within microenvironmental compartments suggests a functional correlation with the events of ovarian development.

Animals↗

PubMed1995

Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.

Animals↗

PubMed1995

The ovarian dysgenesis normally induced by neonatal thymectomy is prevented by the prior administration of estrogen.

PROBLEM: Neonatal thymectomy (Tx) and estrogen (E2) administration disrupt the reproductive and immune systems of female mice. The current experiment examined the combined effects of the two procedures on ovarian function, performed in sequence, and in reverse sequence. METHOD: Groups of (C57BL/6J x A/J)F1 (B6A) female mice were given four daily injections of 20 micrograms estradiol-17 beta, either from 0 days to 3 days, or from 3 days to 6 days postpartum. In some groups this regimen was combined with thymectomy performed either prior to steroid injection (TX-3), or after steroid treatment (TX-4). Animals were sacrificed between 100 and 110 days of age then ovaries evaluated via light microscopy for dysgenesis and follicular cysts. RESULTS: When E2 treatment followed Tx, the incidence of ovarian dysgenesis was unchanged (study 1, Tx + E2 = 60% ovarian dysgenesis; Tx = 63% ovarian dysgenesis) (study 2, Tx + E2 = 46% ovarian dysgenesis; Tx = 45% ovarian dysgenesis). In contrast, when E2 was given before Tx, ovarian dysgenesis did not occur (study 2, E2 + Tx = 0% ovarian dysgenesis; Tx = 46% ovarian dysgenesis). Ovaries from E2 + Tx animals were characteristic of ovaries from E2-injected animals without Tx. CONCLUSION: The results indicate that E2 injection prevents Tx-induced ovarian dysgenesis, suggesting E2-activation of an extrathymic pathway for thymus function.

Animals↗

PubMed1993

Radioligand exchange binding cannot directly determine the dissociation constant (Kd) of the rat ventral prostate nuclear androgen receptor: valid Kd determinations require additional uptake binding data.

Radioligand exchange was examined for its ability to derive the dissociation constant (Kd) of the rat ventral prostate nuclear androgen receptor. In one 24-h, 12 degrees C incubation, Scatchard plot analysis of [3H]dihydrotestosterone ([3H]DHT) exchange binding produced a Kd of 6.9 x 10(-9) M. Specific binding of [3H]DHT ranged from 114 to 758 pM, and the extrapolated value for the total number of binding sites (n) was 1320 pM. When aliquots from the same receptor pool were incubated with unlabeled DHT, and bound androgen was measured by radioimmunoassay, each titration point held a concentration of specifically bound unlabeled DHT little different from the preincubation value of bound endogenous ligand (1338 pM), suggesting that few, if any, unoccupied sites were created during the incubation. In a second radioligand exchange assay, unoccupied receptor sites were measured at the end of incubation. Virtually no unoccupied sites were found, though the range of predicted values was 124 to 383 pM (n = 425 pM). The data, in toto, suggest that although radioactive ligand exchanges with bound unlabeled ligand, the dynamics of the process do not include the creation of unoccupied sites. Since the Kd is determined by measuring the concentrations of unoccupied sites, free ligand, and receptor sites bound to ligand, the absence of unoccupied sites suggests that radioligand exchange cannot be used to directly determine the Kd of the prostate nuclear androgen receptor. The numerical value obtained from radioligand exchange, therefore, instead of being a Kd, is very likely the result of a graphic plot of the increase in specific activity of bound radioligand as [3H]DHT is titrated to higher levels. In the last phase of the study a technique was developed which allows for the correct determination of the Kd of the rat ventral prostate nuclear androgen receptor. For the determination, data from an experiment measuring uptake binding into unoccupied sites were combined with data obtained from radioligand exchange binding. From this, the Kd of the receptor was calculated to be 1 x 10(-12) M.

Animals↗

PubMed1992

Changes in mitochondrial and microsomal 3 beta-hydroxysteroid dehydrogenase activity in mouse ovary over the course of the estrous cycle.

3 beta-Hydroxysteroid dehydrogenase (HSD) is located in the endoplasmic reticulum and mitochondria. To determine whether the separate enzymes play different roles in steroidogenesis, the specific activity (SA) of both were measured at four different stages of the mouse estrous cycle. Microsomal HSD activity changed little throughout, averaging 8.7 +/- 0.7 nmol progesterone/min/mg protein. In contrast, mitochondrial HSD activity changed dramatically at diestrus, increasing to 14.4 nmol progesterone/min/mg protein. When measured at proestrus, estrus, and metestrus, mitochondrial HSD activity was 5.5, 7.4, and 4.5 nmol progesterone/min/mg protein, respectively. To ascertain whether the increase in mitochondrial HSD activity at diestrus could be due to a preferential induction of enzyme, its SA and the SA of a mitochondrial inner membrane enzyme, cytochrome C oxidase, were compared to the SA of a mitochondrial outer membrane enzyme, rotenone-insensitive NADH cytochrome C reductase. The SA of all three enzymes changed proportionally at diestrus, suggesting that the increase in mitochondrial HSD activity was not due to its preferential induction. Rather, we believe that the HSD activity in the mitochondrial fraction, as measured at the four stages of the estrous cycle, is a reflection of the combined contributions from an ever changing population of ovarian cells. Mitochondria from luteal cells have the highest HSD activity, and are very likely responsible for the major synthesis of progesterone during the luteal phase.

3-Hydroxysteroid Dehydrogenases↗

PubMed1991

Cell-mediated and neural control of morphostasis.

Morphostasis refers to the maintenance of the differentiated state of tissues in an adult individual and it represents a basal event of homeostasis and the organism's existence. Most of the cells in the body are arrested in their differentiation at a certain point related to their optimal function. Evidence is rapidly accumulating on the general role of immunoglobulin-gene superfamily (IGSF) domains in the non-immune control of behavior of cells in various tissues. A novel 'tissue control system' (TCS) has been suggested, supporting the differentiation of tissue cells in an adult organism and functioning via the IGSF domains and cell-mediated control of morphostasis. We assume here that the morphostasis is established epigenetically during the early adaptive period. With its termination, coinciding with the attainment of an organism's immunocompetence, the combination of cell surface markers of the most mature cells in tissues are encoded in the TCS as the stop-signal (SS). This stage of tissue differentiation is maintained during further life: upon recognition of SS the committed TCS element does not stimulate further differentiation of the cell, i.e. it exhibits a stop-effect (SE). Each tissue-specific cell line has only one or no SE established depending on its presence or absence during development, respectively. The only way to escape an established SE and continue in differentiation is to change at least a portion of the SS. Hormones might act here directly, by conformation of their cell surface receptors recognized as a portion of SS, or indirectly, by influencing proteosynthesis of cell surface markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Nocturnal illumination does not necessarily stimulate the photoperiodic response, despite mimicking the effects of constant light on the circadian system in the male Syrian hamster.

In an effort to determine the inductive component(s) of photic input in long day seasonal breeders, adult male Syrian hamsters (Mesocricetus auratus) were exposed to one of nine lighting conditions for a duration of 10 weeks: a light-dark cycle of 14 hours of light followed by 10 hours of dark (LD 14:10, a long photoperiod); LD 10:14 (a short photoperiod); a high frequency light-dark cycle of 1 hour of light and 1 hour of dark (LD 1:1); a higher frequency light-dark cycle of 1 minute of light and 1 minute of dark (LD 1m:1m); constant light (LL); constant dark (DD); feedback lighting (LDFB; a condition that illuminates the cage in response to locomotor activity); a feedback lighting neighbor control (LDFB NC; the animal receives the same light pattern as a paired animal in LDFB, but has no control over it); or reverse feedback lighting (rLDFB; a condition that darkens an illuminated cage in response to locomotor activity). Exposure to LL, LD 1:1, LD 1m:1m, LDFB and rLDFB significantly and similarly lengthened the free-running period of the locomotor rhythm when compared to the period of animals in DD. The paired tests and accessory reproductive glands weights, spermiogenesis, seminiferous tubule diameter and serum concentrations of testosterone, prolactin, LH and FSH, suggest that LD 14:10, LL, LD 1:1, rLDFB and LDFB NC maintain reproductive function in the Syrian hamster, while LD 10:14, DD, LD 1m:1m and LDFB do not. It is known that as little as two 1-second pulses of light are stimulatory if coincident with the subjective night (17.22). Thus, it is not surprising that LD 1:1 is stimulatory. LD 1m:1m is not stimulatory, however, despite an identical quanta of light per 24 hours and similar phase relationship. It appears that mere light exposure during the subjective night is not necessarily reproductively inductive. It would also appear that behaviorally generated light-dark cycles can be (i.e., LDFB), but are not necessarily (i.e., rLDFB) inhibitory to the maintenance of the reproductive system in long day breeders. Furthermore, the lighting pattern derived from LDFB is stimulatory if given exogenously (i.e., LDFB NC). Although it is not understood why light exposure that is coincident with the subjective night (i.e., LD 1m:1m and LDFB) is not stimulatory in long day breeders, a possible hypothesis is that an internal coincidence model is involved in the photoperiodic response and that multiple transitions during the subjective night may cause a dissociation of internal oscillations which must be in phase for light to be stimulatory.

Animals↗

PubMed1990

Neonatal thymectomy affects follicle populations before the onset of autoimmune oophoritis in B6A mice.

Using a variation on a standard follicle classification technique, 5 classes of follicles were quantified in serial sections of ovaries from intact mice and mice thymectomized on Day 3 at 5-day intervals from 5 to 40 days of age. Sera from these animals and from animals 60 days of age were analysed for the presence of anti-oocyte antibodies. Ovaries from intact animals 10 to 40 days of age were examined for the presence of antigen(s) using anti-oocyte antibody-positive sera from all ages of mice. There was a dramatic decrease in the primordial follicle population at 10 days of age in thymectomized mice and that population remained significantly lower until 40 days of age. The growing follicle population was also significantly lower at 20 days of age in thymectomized mice and remained lower through 40 days of age. Anti-oocyte antibodies were not detectable until 30 days of age and at that age reacted with oocytes from all follicle types including primordial. Ovarian antigens were present in similar patterns in ovaries from mice at all ages tested. We conclude that thymectomy has an earlier influence on the ovary than previously thought and this influence does not appear to involve the immune activity associated with autoimmune ovarian dysgenesis. This suggests that the effect of thymectomy on the ovary may be biphasic: (1) an early effect, possibly involving a disruption in the hypothalamic-pituitary-ovarian-thymic axis, that influences the primordial and growing follicle populations before 20 days of age; and (2) a later effect involving an immune imbalance first evident by 25-30 days of age that ultimately results in the destruction of the ovary.

Animals↗

PubMed1990

Plasma protein and hormone profiles associated with autoimmune oophoritis and ovarian tumorigenesis in neonatally thymectomized mice.

Interactions between the immune and endocrine systems may have an important role in ovarian tumorigenesis. Neonatal thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J)F1 (C31) female mice results in an autoimmune ovarian dysgenesis then subsequent tumor formation. At 3 months of age the histology of the ovaries showed that approximately 60% of the Tx-3 mice (Tx-3 DO) had completely lost their oocytes and follicles so that a preponderance of interstitial-like cells remained. The remainder of the Tx-3 mice had atypical ovaries (Tx-3 AO). The vaginal cytology showed that both groups of Tx-3 mice became acyclic at an early age compared to the intact mice. Around 12 months of age, a high percentage of the dysgenic ovaries developed trabecular tumors. Plasma protein-related indicators of systemic inflammatory responses showed little change during the course of the autoimmune oophoritis or ovarian tumorigenesis. Levels of estradiol 17 beta (E2) and testosterone (T) did not vary in the Tx-3 mice compared to those of the intact mice through 21 months of age but progesterone levels were lower during the exacerbation of the autoimmune oophoritis and tumor development. By 24 months of age levels of P increased while E2 decreased. Apparently, the premature reproductive failure in these mice at a young-adult stage results from the early loss of the oocytes by the localized autoimmune insult to the ovaries. The autoimmune oophoritis may then be the primary trigger for the subsequent ovarian tumor formation and the tumors succeed in association with the altered hormonal milieu.

Aging↗

PubMed1989

Aromatase activity in cultured ovaries from neonatally thymectomized mice with ovarian dysgenesis.

The autoimmune oophoritis resulting from thymectomy at 3 days of age (Tx-3) in B6A female mice is characterized by dysgenic ovaries and circulating auto-antibodies against the oocyte (AOA). Dysgenesis of the ovaries starts around 24 days of age with a decline in numbers of the oocytes and follicles and is accompanied by lymphocytic infiltration. By 60 days of age the ovarian dysgenesis (OD) is complete with a preponderance of interstitial cells associated with elevated levels of testosterone (T). From 60-120 days of age the ovaries become progressively smaller in size and T levels rise. Since ovarian interstitial cells can produce T, assessment of aromatase activity was determined using cultured ovaries from 20-, 30-, 60-, 90- and 120-day-old mice. Similar or enhanced ability in aromatizing T to estradiol-17 beta (E2) was demonstrated by the ovaries from all Tx-3 mice compared with those from intact mice. At 30 and 60 days of age Tx-3 mice had increased circulating levels of E2 then the levels of E2 returned to those of intact mice at 90 and 120 days of age. The results indicate that the ovaries in Tx-3 mice may have an ability to aromatize T to E2 in culture, but apparently are not doing so at 90 and 120 days of age in situ. Further, ovaries of Tx-3 animals are able to aromatize T to E2 in the absence of organized follicular cells. These abnormal responses of ovarian hormones clearly demonstrate that the presence of AOA have a damaging effect on the endocrine activity as well as the morphology of the ovary.

Animals↗

PubMed1988

Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice.

Groups of female C3H/HeMs x 129/J F1 mice were given injections of either 20 micrograms of 17 beta-estradiol or sesame oil (vehicle) for the first 5 days after birth. Half of each group was then given gastric intubations of 20 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) at 70, 77, and 84 days of age. The other half of each group was given sesame oil. Thus, this design yielded four experimental groups: oil + oil; 17 beta-estradiol + oil; oil + DMBA; and 17 beta-estradiol + DMBA. They were sacrificed at approximately 144 days of age (Experiment 1) or the day of palpable ovarian tumor detection or 360 days of age (Experiment 2). In Experiment 1, the total number of oocytes (follicles) per ovary in mice of the 17 beta-estradiol + oil group was maintained at the same level as mice of the oil + oil group. A significant reduction of oocytes, however, was observed in mice of the 17 beta-estradiol + DMBA group in comparison with mice of the oil + DMBA group (P less than 0.01), and neoplastic nodules of the granulosa cell type developed in the unilateral ovary in 10 of 17 mice of the 17 beta-estradiol + DMBA group. No tumors were detected in the mice of the other groups. The plasma levels of both follicle-stimulating and luteinizing hormones as determined by radioimmunoassay were significantly higher (P less than 0.01) in mice of the 17 beta-estradiol + oil group than in mice of the oil + oil group. In Experiment 2, more ovarian tumors of the granulosa cell type were detected before 360 days of age in mice of the 17 beta-estradiol + DMBA group (14 of 18) than in mice of the oil + DMBA group (5 of 15) (P less than 0.05). No tumors developed in mice of the other two groups. These results strongly indicate that an abnormal endocrine milieu caused by neonatal treatment with estrogen may induce a high frequency of transformation of some ovarian tissues and rapid growth of the ovarian tumors after DMBA treatment.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1988

Hormonal characterization of female SL/Ni mice: a small thymus gland strain exhibiting ovarian dysgenesis.

Female SL/Ni mice have a small thymus gland and show accelerated aging of the reproductive system characterized by an early loss of the follicular apparatus and early onset of ovarian tumors. At 9 months of age, circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were higher in the SL/Ni animals than in controls while prolactin (PRL) was lower in the SL/Ni mice. The trends of these hormones are consistent with the loss of the follicular apparatus which is responsible for estradiol production. The high levels of gonadotropins which precede the onset of the tumors confirm the hypothesis that prolonged stimulation by gonadotropins can be a cause of ovarian tumorigenesis. Further, these data suggest that aging of the reproductive system may be a thymus-dependent phenomenon.

Aging↗

PubMed1988

Source of high testosterone levels associated with autoimmune ovarian dysgenesis in neonatally thymectomized B6A mice.

Thymectomy at three days of age (Tx-3) in mice results in early ovarian dysgenesis and eventual sterility. In (C57BL/6JCr x A/JCr)F1 (B6A) mice, the ovaries are reduced in weight, composed mostly of interstitial-like cells, and are usually devoid of oocytes, follicles, and corpora lutea by 60 days of age. This thymectomy-induced acceleration of follicular atresia is autoimmune in nature and is accompanied by circulating auto-oocyte antibodies (AOA). The dysgenesis is also characterized by elevated levels of testosterone (T). To determine the source of these high T levels, various combinations of Tx-3, and adrenalectomy (Adx) and ovariectomy (Ovx) at 15 days of age were performed. Levels of T, estradiol-17 beta (E2), and corticosterone (B) were analyzed and compared with ovarian morphology. Except for plasma B levels, animals that underwent both Tx-3 and Adx were not significantly different from mice that received Tx-3 alone. As anticipated, B and E2 levels were substantially decreased in Adx and Ovx mice, respectively. T levels in the Tx-3 and Tx-3/Adx groups were first elevated at 60 days of age (0.17 and 0.14 ng/ml, respectively) then rose sequentially through 150 days of age (0.91 and 0.89 ng/ml, respectively) as compared to the significantly lower T levels in intact and Tx-3/Ovx mice (less than 0.20 ng/ml through 150 days of age). These results suggest that the increased T is being secreted by ovarian rather than adrenal tissue. Furthermore, this model may be of value to investigators interested in the study of interstitial or non-follicular steroidogenesis in the ovary.

Adrenal Glands↗