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Clinical and endocrinologic manifestations in perinatally human immunodeficiency virus type 1--Infected children aged 5 years or older.

Sixteen human immunodeficiency virus type 1 (HIV-1)-seropositive children aged 5 to 12 years (nine girls and seven boys), born to HIV-1-infected mothers, were diagnosed between 1984 and 1987 in Kigali, Rwanda. They were compared with a group of age- and sex-matched HIV-1-seronegative children consecutively selected from the outpatient department. Two subjects were asymptomatic. Chronic cough was the most frequent symptom (seven of 16 patients). The most common signs were short stature (12 of 16 patients), low weight for age (seven of 16 patients), chronic parotitis (eight of 16 patients), persistent generalized lymphadenopathy (seven of 16 patients), and pulmonary tuberculosis (four of 16 patients). Lymphoid interstitial pneumonitis was diagnosed on radiologic grounds in five of 16 patients. Evidence of perivasculitis in the fundus was noted in three of 16 patients. Two children died during the study period (mean duration of follow-up, 40 months; range, 27 to 62 months); none of the other children had life-threatening infection or loss of developmental milestones. Immunologic assessment in the 16 children revealed high levels of IgG, decreased CD4+/CD8+ ratio, and skin test anergy. Endocrinologic investigations revealed normal thyroid function and normal basal human growth hormone levels but low basal insulinlike growth factor I levels (0.21 +/- 0.07 vs 0.44 +/- 0.20 U/mL for controls). In Kigali, perinatally HIV-1-infected children surviving beyond 5 years of age often present with moderate signs and symptoms, principally pulmonary involvement, chronic parotitis, and persistent generalized lymphadenopathy. Short stature is the major clinical manifestation in these patients and may be due, in part, to low growth hormone secretion rather than to malnutrition.

Body Height↗

Reproductive endocrinology of female elasmobranchs: lessons from the little skate (Raja erinacea) and spiny dogfish (Squalus acanthias).

Conventional classification of reproductive modes in female elasmobranchs fails to account for the diversity in ovarian dynamics that operate during oviparous and viviparous cycles. Delineating this diversity is crucial for understanding the endocrine regulation of the manifold physiological mechanisms utilized to retain and protect eggs and developing embryos, to fuel embryogenesis, and to manage the intrauterine milieu. Oocyte development and follicular steroidogenesis overlap with egg retention and pregnancy in some species, whereas in others the follicular phase of the cycle is temporally separated from the gravid period. A luteal phase predominates the post-ovulatory period in viviparous species. In oviparous species, the luteal phase overlaps with the follicular cycle. This heterogeneity in ovulatory cycles suggests that the endocrine system evolved a transmutable system for regulating steroidogenesis and the control of the reproductive events. The reproductive biology and endocrinology of the oviparous little skate and lecithotrophic viviparous spiny dogfish are reviewed in order to derive a working hypothesis that explains the complex nature of endocrine patterns observed in species utilizing disparate reproductive modes. An understanding of the adaptations in ovarian dynamics to particular ovulatory cycles is key to developing theories about the evolution of reproductive strategies in female elasmobranchs. J. Exp. Zool. 284:557-574, 1999.

Animals↗

Clinical, magnetic resonance imaging and endocrinological differences between delusional and non-delusional depression in the elderly.

OBJECTIVE: To investigate neuroradiological, endocrinological and clinical differences between delusional and non-delusional depression. DESIGN: A cross-sectional study of depressed subjects. SETTING: Melbourne, Australia. PARTICIPANTS: Sixty-one subjects (inpatients) over the age of 55 meeting DSM-III-R criteria for major depression of whom 22 had delusional subtype of depression. MEASURES: Clinical assessment, including documentation of vascular risk factors. Cognitive assessment by the Cambridge Cognitive Examination (CAMCOG). Magnetic resonance imaging (MRI) scans were performed on a 0.3 Tesla scanner with temporal lobe atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) rated visually on 4-point scales. A standard 1 mg dexamethasone suppression test (DST) was performed. RESULTS: Subjects with delusional depression had significantly more vascular risk factors than those without delusions. There were no differences in measures of temporal lobe atrophy, PVL, DST results or cognitive test scores, though there was a non-significant trend for DWML to be more prevalent in those with delusions. Delusional depression was associated with a shorter duration of history and more frequent treatment with ECT. CONCLUSIONS: The increase in vascular risk factors and trend towards greater DWML on MRI suggests an organic contribution to delusional depression in the elderly. In contrast to some previous reports, we found no differences in cortical MRI appearance or neuroendocrine measures between groups.

Aged↗

Neuroendocrine carcinoma of the paranasal sinus: a morphological and endocrinological study.

Four cases of small cell carcinoma of the paranasal sinuses were studied histologically, ultrastructurally, and endocrinologically. All tumors showed features of undifferentiated carcinoma with alveolar patterns but without acinar or squamous differentiation and contained cells possessing endocrine-type small secretory granules, which were indistinguishable from non-neoplastic neurosecretory granules. The three cases also possessed a small number of microtubules, and in one of these fine cytoplasmic filaments were observed. One case showed elevated plasma levels of cortisol and adrenocorticotropic hormone associated with adrenocortical hyperplasia and Crooke's changes of the pituitary gland. Another case showed hypercalcemia with bone metastasis, hypercalcitonemia with a high content of calcitonin in the tumor tissue, calcitonin-positive tumor cells, and C-cell hyperplasia of the thyroid. It was concluded that all four cases should be called neuroendocrine carcinoma, which might be related to neoplasms derived from amine precursor uptake and decarboxylation cell series rarely encountered in the paranasal sinuses.

Adrenocorticotropic Hormone↗

Endocrinologic basis of electrochemical vaginal potential in estrous cycle of rats.

This sequel to an earlier report on the correlation of vagino-oral voltage measurements in rats with their estrous cycles deals with the endocrinologic activation of these voltages. The normally sinusoidal voltages, positive during estrus and negative during diestrus, were absent in spayed rats but were restored with a single intraperitoneal injection of 5 microgram or more of 17beta-estradiol or with 0.1 mg of adrenaline injected subcutaneously every 12 hours. Estrogen antagonists, drugs that inhibit catecholamine synthesis or adrenergic beta blockers, totally inhibit the negative potential recorded during estrus. Vaginal estrous potentials in the rat reflect an important reproductive state possibly linked to sexual behavior (heat) or to ovulation. Triggering of the cyclic potential by adrenaline without estrogenic medication suggests that adrenaline belongs to the group of sexual-specific hormones.

Animals↗

The musk shrew, Suncus murinus, a unique animal model for the study of female behavioral endocrinology.

Insectivora is the third largest mammalian order, composed of a number of unusual species considered to be the most primitive of the modern eutherian mammals. Yet, little is known about the members of this evolutionarily unique and important group. The musk shrew (Suncus murinus) is a convenient and practical laboratory animal. The study of the reproductive biology of this species will yield needed comparative data. Moreover, the little information that we have collected on this species suggests that several unusual characteristics make this animal a worthwhile and novel model for endocrine research. Most of the current and past research on this species has focused on the endocrinology of the female musk shrew. Unlike conventional small mammal models, the female musk shrew has no spontaneous ovarian cycle. The ovaries of the adult, unmated female do not undergo spontaneous follicular development. At the time of mating only small, relatively immature follicles are present. As a consequence, ovarian hormone production is not cyclic. Thus, traditional hormone target tissues such as the vaginal epithelium and the uterus do not exhibit cycles in cell proliferation. Sexual behavior is likewise demonstrated in an acyclic manner. Virgin females become sexually receptive within minutes after their first exposure to a male, and nonpregnant females are virtually always sexually receptive. Sexual receptivity in the virgin female musk shrew occurs in the face of relatively low plasma estradiol levels and higher androgen levels, and does not appear to be mediated via ovarian estradiol. Instead, recent work suggests that close to physiological doses of testosterone can restore sexual behavior in ovariectomized musk shrews.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contribution of comparative fish studies to general endocrinology: structure and function of some osmoregulatory hormones.

Fish endocrinologists are commonly motivated to pursue their research driven by their own interests in these aquatic animals. However, the data obtained in fish studies not only satisfy their own interests but often contribute more generally to the studies of other vertebrates, including mammals. The life of fishes is characterized by the aquatic habitat, which demands many physiological adjustments distinct from the terrestrial life. Among them, body fluid regulation is of particular importance as the body fluids are exposed to media of varying salinities only across the thin respiratory epithelia of the gills. Endocrine systems play pivotal roles in the homeostatic control of body fluid balance. Judging from the habitat-dependent control mechanisms, some osmoregulatory hormones of fish should have undergone functional and molecular evolution during the ecological transition to the terrestrial life. In fact, water-regulating hormones such as vasopressin are essential for survival on the land, whereas ion-regulating hormones such as natriuretic peptides, guanylins and adrenomedullins are diversified and exhibit more critical functions in aquatic species. In this short review, we introduce some examples illustrating how comparative fish studies contribute to general endocrinology by taking advantage of such differences between fishes and tetrapods. In a functional context, fish studies often afford a deeper understanding of the essential actions of a hormone across vertebrate taxa. Using the natriuretic peptide family as an example, we suggest that more functional studies on fishes will bring similar rewards of understanding. At the molecular level, recent establishment of genome databases in fishes and mammals brings clues to the evolutionary history of hormone molecules via a comparative genomic approach. Because of the functional and molecular diversification of ion-regulating hormones in fishes, this approach sometimes leads to the discovery of new hormones in tetrapods as exemplified by adrenomedullin 2.

Adrenomedullin↗

Transgenic strategies in reproductive endocrinology.

The present discussion surveys some of the recently published studies utilizing transgenic strategies to address questions in reproductive endocrinology. Beginning with a brief introduction of the transgenic method itself, the following areas are covered: 1. Sexual development and Müllerian-inhibiting substance; 2. Hypogonadal mice and hypothalamic GnRH; 3. The GnRH neuron: generation of immortalized rare cell types; 4. Glycoprotein hormones: immortalized cells, development and evolution; 5. Growth hormone and reproduction; and, 6. Gestation and the insulin-like growth factors. In each section, the discussion attempts to be integrative with respect to the significance of the results to physiological, cellular and molecular biology. We believe this approach is appropriate, as transgenic science itself is necessarily an integration of all of these levels of investigation and participation from those working at all levels is needed.

Animals↗

Tandem duplication of DMD exon 18 associated with epilepsy, macroglossia, and endocrinologic abnormalities.

We describe a patient with Duchenne muscular dystrophy (DMD) who additionally suffered from intractable seizures, severe mental retardation, and a marked macroglossia. He also had endocrinologic abnormalities consisting of growth hormone deficiency, delayed puberty, and adrenal hypoplasia. We detected a duplication of DMD exon 18 and flanking introns that caused a frame-shift and was not removed by corrective splicing. A coincident mutation in the FKRP gene was excluded by direct sequencing. Complex DNA rearrangements, deletions, and duplications >100 kb were excluded through microarray-comparative genomic hybridization (CGH), although we were not able to exclude a second coincident mutation with certainty. In conclusion, we present a case of DMD that conflicts with current understanding of genotype-phenotype relations and discuss putative pathogenetic mechanisms for this uncommon phenotype.

Adrenal Insufficiency↗

The use of genetic "knockout" mice in behavioral endocrinology research.

The production of mice with specific deletion of targeted genes (knockouts) has provided a useful tool in understanding the mechanisms underlying behavior. There are many opportunities with this new tool for behavioral neuroendocrinology, specifically, and behavioral biology, generally. Although this genetic technique offers new opportunities to study the mechanisms of behavior, as with all behavioral techniques there are some potential limitations. For example, the products of many genes are essential to normal function, and inactivating the gene may prove lethal or induce gross morphological or physiological abnormalities that can complicate interpretation of discrete behavioral effects. Unexpected compensatory or redundancy mechanisms might be activated when a gene is missing and cloud interpretation of the normal contribution of the gene to behavior. Behavioral tests study the effects of the missing gene (and gene product), not the effects of the gene directly. This conceptual shortcoming can be overcome in the same way that it is overcome in other types of ablation studies, by collecting converging evidence using a variety of pharmacological, lesion, and genetic manipulations. Finally, because mammalian genome mapping is currently focused on mice (Mus musculus), standardized behavioral testing of mice should be adopted. Against those disadvantages are several important advantages to using knockout mice in behavioral research: (1) disabling a gene is often a very precise and "clean" ablation, (2) the effects of the gene product can be abolished without the side-effects of drugs, and (3) genetic manipulations may be the only way to determine the precise role of many endogenous factors on behavior. The use of new inducible knockouts, in which the timing and placement of the targeted gene disruption can be controlled, will be an extremely important tool in behavioral endocrinology research.

Animals↗

Differential behavioral and endocrinological effects of corticotropin-releasing hormone (CRH) in the Syracuse high- and low-avoidance rats.

The Syracuse high- and low-avoidance rats, which have been selectively bred for good (SHA/Bru) or poor (SLA/Bru) avoidance learning in a two-way shuttle box, differ in emotionality. This experiment investigated the effect of corticotropin-releasing hormone (CRH), administered centrally (0, 0.1, 0.5, and 1.0 microg), on conditioned suppression and on the hypothalamic-pituitary-adrenocortical system. Three groups of animals were used: SHA/Bru rats conditioned at 0.21 or 0.43 mA and SLA/Bru rats conditioned at 0.21 mA. The results confirm those of previous studies which found that SLA/Bru rats show greater conditioned suppression than the SHA/Bru rats at the low shock intensity and that at 0.43 mA, the SHA/Bru animals acquire a level of conditioning comparable to that of the SLA/Bru animals at 0.21 mA. The results show that the nonlinear behavioral effect of CRH is independent of strain and produces comparable effects in animals of both strains, but only when level of conditioning is equated. Adrenal and plasma concentrations of corticosterone increased in all three groups of animals as a direct linear function of dose of CRH. Both greater levels of conditioning and larger amounts of CRH increase the synthesis of corticosterone more in SHA/Bru animals than in the SLA/Bru animals. Thus, genetic variation, which differentiates the behavioral and endocrinological characteristics of these animals, shows that these effects of CRH can be independent of each other and suggests that some minimal level of conditioned fear is necessary for CRH to exert its anxiogenic effect.

Acoustic Stimulation↗

The endocrinology of testicular tumors.

The endocrine manifestations of testicular tumors can be produced by one of three mehcansims: (1) direct synthesis of androgens or estrogens by the tumors; (2) synthesis of gonadotropins that stimulate secondary secretion of androgens or estrogens; (3) alteration of the peripheral metabolism of androgens. In this manuscript we have discussed these mechanisms in relationship to steroid-secreting tumors and gonadotrepin-secreting tumors. In postpubertal males, the most common manifestation of these tumors is the production of gynecomastia. Because the breast is a target organ for the action of both androgens and estrogens, gynecomastia occurs when there is an alterartion in the normal androgen/estrogen ratio. Consequently, gynecomastia may be produced by either deficient androgen production or excessive estrogen secretion. The endocrinology of testicular tumors is a fascinating subject and recent development of sensitiv specific radioimmunoassays for the measurement of tumor markers has opened a new area of investigation into the biology of these neoplasms.

Androgens↗

Peptides and the new endocrinology.

The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

Adrenocorticotropic Hormone↗

Light- and electron-microscopic features of an endocrinologically active pituitary adenoma cultured in vitro.

A pituitary adenoma from an acromegalic female patient has been studied in cell cultures. Two populations of parenchymal cells, i.e., elongated shapes and big pale forms with irregular outlines, were distinguished light-microscopically. Ultrastructurally, three types of cells were found. Two of them contained secretory granules in varying numbers and sizes. Based on the proportion of the various cellular elements these cells were considered as counterparts of the elongated shapes being responsible for the GH secretion at different rates. The third cell type with very few secretory granules was identified with the big pale forms. Presumably, they could be exhausted GH-secreting cells. Besides fine structural characterisation, cultured cells of endocrinologically active human pituitary adenomas offer suitable models for studying some phases of exocytosis and membrane retrieval.

Acromegaly↗

[Endocrinology of the climacteric].

The endocrinology of the menopause is determined by the decrease of estrogens. In 250 healthy patients there was an observed decrease of estrone to 35 pg/ml and of estradiol to 10 pg/ml serum between the 49th and 54th year of age. Thereafter no further decline occurred, because the androgen precursors of the estrogens were secreted by the adrenal cortex until advanced age. In a period of 30 years there was a decrease of the androgen levels of only 25%. In 200 patients with severe obesity we found no differences in peripheral steroid concentrations, but the SHBC concentrations were significantly lowered; therefore, the amount of free active estradiol and the effect on the target organ is higher in these patients.

Climacteric↗

From Endocrinology to Intracrinology.

Recently, in situ formation of active sex steroids at the sites of their actions from biologically inactive precursors in the circulation have been demonstrated to play very important roles in sex steroid-dependent neoplasms. These tissues in which the conversion occurs are designated as intracrine tissues and their mechanisms of actions can be designated as intracrinology in contrast to endocrinology. Aromatase, which converts serum androgens to estrone, and 17B-hydroxysteroid dehydrogenase I, which is involved primarily in the conversion of estrone to estradiol, are two major enzymes which function in the in situ formation of biologically active estrogens from circulatory androgens. In human estrogen-dependent neoplasms, including breast, endometrioid endometrial, and common epithelial ovarian carcinoma, we recently demonstrated overexpression of aromatase, especially in stromal cells at sites of frank invasion possibly under a new promoter usage and that of 17B-hydroxysteroid dehydrogenase I in these carcinoma cells. These estrogen-dependent carcinomas are considered to have a common characteristic in estrogen metabolism (i.e., the expression of aromatase in the stromal cells and of 17B-hydroxysteroid dehydrogenase I in the epithelial cells). With these in situ mechanisms of generating biologically active estrogens from circulating androgens, that is, "intracrine manner," these estrogen-dependent neoplasms can exert estrogenic actions on carcinoma cells despite low circulating serum estrogen levels, as observed in postmenopausal women. Evaluation of intracrine mechanisms can provide new insights into various estrogen-related biological phenomena in humans.

Journal Article↗

Endocrinological parameters in experimental unilateral undescended testis.

It is a common clinical practice to estimate FSH, LH and testosterone levels in patients with unilateral undescended testis (U/L UDT) as a prognostic pointer to fertility potential. Is this practice correct? To ascertain this aspect, new born rats were operated to create experimental U/L UDT by gubernaculectomy and anchoring the gubernaculum to anterior abdominal wall. Fertility and hormone levels were evaluated later in adult life. Though fertility of rats with U/L UDT was significantly less (p < 0.01) than the controls, no significant alterations were found in the levels of serum testosterone, FSH and LH. Even though variations in the hormone levels may be responsible, to a certain extent, for the decrease in fertility potential in U/L UDT, estimation of sex hormone levels in U/L UDT is not a sensitive indicator of fertility potential. U/L UDT may additionally be affecting fertility through non-endocrinological mechanisms.

Animals↗

Clinical implications of trace elements in endocrinology.

The implications of essential trace elements in endocrinological processes, mainly thyroid function, growth, gonadal function, adrenal hormones, prolactin, glucose homeostasis, calcium-phosphorus metabolism, and thymulin activity, are reviewed. Most concerned elements in this field include iodine, zinc, selenium, copper, chromium, manganese and vanadium. The minerals are powerful modulators of several physiological functions that can be considerably perturbed in deficiency states. The resulting biochemical and clinical modifications can be prevented and/or corrected by adequate supplementation. Sometimes, however, they act like pharmacological agents when their beneficial effects are not the result of a correction of a nutritional deficiency state. Their potentialities as therapeutic agents are perfectly described in many cases, but some indications deserve further investigations.

Adult↗