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Biomedical subjects

F Larrea

Publications and source records attributed to F Larrea.

At least 73 records · Page 4Linked to original sources

Hypothalamic hypogonadism in myotonic dystrophy.

Hypothalamic-pituitary-ovarian axis function was assessed in a postpubertal female patient with myotonic dystrophy and secondary amenorrhea. The results suggested a hypothalamic basis for the amenorrhea, confirming previous reports regarding the nature of gonadal failure in women with this multisystemic disorder.

Adult↗

Cytogenetic and endocrine studies in a 45,X female subject with spontaneous sexual development.

Cytogenetic and endocrine evaluation of a postpubertal 45,X female subject with Turner's stigmas and spontaneous sexual development was performed. A 45,X chromosomal complement was found in the peripheral blood lymphocytes, bone marrow, and fibroblasts derived from skin and ovaries. Menarche, pubarche, and thelarche occurred at age 12; at age 16 she developed menstrual irregularities, with endometrial bleeding occurring every 60 to 90 days. The ovaries were normal in size, and histologic examination revealed a marked paucity of primordial follicles, increased collagenization, and absence of corpora albicans. Anovulatory cycles with moderately elevated levels of luteinizing hormone (LH) and low follicle-stimulating hormone (FSH) levels were observed. LH-releasing hormone pituitary stimulation induced a normal LH release with a very slight FSH increase. Administration of clomiphene citrate successfully induced a normal-length ovulatory cycle. Similarities in the hormonal situation of this patient and that seen in the Stein-Leventhal syndrome are pointed out.

Adolescent↗

[Crohn's disease in childhood. Comments on one case (author's transl)].

Chronic inflammatory diseases of the bowel are specially frequent in the adult, with peak incidence during adolescence and early adulthood. There are, however, increasing number of reports in the pediatric age group, mainly coming from anglosaxon countries although more recently also from countries of Southern Europe. Authors present a case of Crohn disease occuring in a child, with typical clinical, radiological and pathological features, since they are not aware of any report in the Spanish literature. Comments are made upon pathogenesis, clinical features and pathological findings and specially upon the treatment established in the present case in relation with the indications of other authors.

Child↗

Gynecomastia as a familial incomplete male pseudohermaphroditism type 1: a limited androgen resistance syndrome.

Four postpubertal 46 XY male patients with an inherited form of bilateral gynecomastia were studied to delineate the nature of the disease. Normal serum FSH and moderately elevated serum LH with concomitantly increased circulating levels of testosterone (T) and estradiol (E2) were found persistently in all cases in blood samples drawn at frequent intervals. LRH pituitary stimulation resulted in an exaggerated LH response and a normal FSH response. Chronic administration of T-cyclopentylate failed to decrease serum LH levels. The peripheral conversion rate of androstenedione to estrone was within normal limits. All patients had low ejaculate volumes with relatively normal spermatozoa counts. Testicular biopsies revealed normal Leydig cells and complete spermatogenesis. Urological examination disclosed that the prostate gland was extremely small. The breast tissue demonstrated the presence of tubular structures as well as the specific binding of [3H]T and [3H]dihydrotestosterone (DHT), which was inhibited by nonlabeled T, DHT, E2, and progesterone, but not by cortisol. The pedigree suggested a recessive X-linked inherited trait. A patient with a nonfamilial form of gynecomastia served as a control in all studies. These data were interpreted as demonstrating that this inherited type of gynecomastia represents the mildest expression of the androgen resistance syndromes and, therefore, belongs to the type 1 form of familial incomplete male pseudohermaphroditism.

Adolescent↗

Anorchia and persistent Müllerian duct: a variant of the embryonic testicular regression syndrome.

A 20-yr-old phenotypical male with a 46, XY chromosome complement, a hernia uteri inguinale, and bilateral anorchia was studied. Eunochoidal body proportions, infantile type of male external genitalia with empty scrotum, underdeveloped sexual characteristics, and delayed bone age suggested the existence of inadequate testicular function. Extremely low levels of circulating testosterone and a lack of response to hCG stimulation was found. Persistently elevated blood levels of LH and FSH with an adequate pituitary response to an iv bolus of synthetic LRH was demonstrated, thus indicating inadequate endocrine gonadal function as well as functional integrity of the hypothalamic-pituitary unit. At the time of an inguinal hernioplasty, a small but well developed uterus was removed. No gonads were found within the true pelvis, inguinal canals, or along the anatomical pathways of testicular descent. A cord-like structure found in the left inguinal canal contained only fibrous tissue without gonadal elements. It is proposed that the occurrence of two altered events during embryogenesis, failure of Müllerian duct regression and late testicular regression, may explain the underlying defect in this unusual abnormality of sexual differentiation.

Adult↗

Comparative study of serum luteinizing hormone levels in human subjects as measured by radioimmunoassay and radioreceptorassay.

A rapid, precise, sensitive, and specific radioreceptorassay (RRA) for serum luteinizing hormone (LH), using a 15,000 X g pellet from bovine corpora lutea, was developed. A comparative study of the serum LH levels in human subjects as measured by this RRA and by radioimmunoassay (RIA) using the same standard preparation was then conducted. The serum LH profile throughout the entire menstrual cycle and the pituitary responsiveness to LH-releasing hormone (LH-RH) stimulation during the two phases of the cycle were studied in two normal women. In addition, LH levels in two normal postpubertal men were measured in blood samples obtained before and after LH-RH administration. Similar, although not identical, LH profiles were found in all cases by both hormone assay methods. Higher RRA-assayable LH values were obtained throughout the menstrual cycle as compared with those obtained by RIA. A significant LH-RH pituitary response in terms of LH in both RRA and RIA during the luteal phase was observed as compared with that observed during the early follicular phase. In the two normal men, the LH values obtained with RRA were higher than those obtained with RIA. It is concluded that the LH RRA is a practical and efficient tool for clinical research.

Adult↗

Estrogenic effects of the synthetic aminoestrogen 17 beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol (pentolame).

In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in the castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the vehicle alone daily for 5 consecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased significantly (p < 0.05) the blood clotting time when compared with that obtained in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000 micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH levels (IC50 860 micrograms), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependent progestin binding sites at the anterior pituitary level. The affinity constants and the number of binding sites of pentolame-induced progestin receptors were similar to those obtained with estradiol at equipotent doses (860 micrograms vs. 1 microgram/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant increase in uterine weight (EC50 420 micrograms) and endometrial characteristics were indistinguishable from those observed in the group of rats treated with E2.

Amino Alcohols↗

G protein-coupled receptors as targets for prolactin actions.

Prolactin (PRL) is known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, and immunomodulation. The first step in PRL action involves its interaction with a specific membrane receptor that belongs to the cytokine receptor superfamily. In spite of the lack of a kinase domain, receptors of the cytokine superfamily induce tyrosine phosphorylation of cellular substrates including the receptors. The role of PRL in female reproductive functions is well known and a direct effect on ovarian and testicular steroidogenesis has been established. In the ovary, PRL binds to a specific membrane receptor and exerts an inhibitory effect on follicular steroidogenesis. This effect is the result of an impairment involving FSH stimulation of G protein-coupled receptors (GPCR) and cyclic AMP-mediated activation of aromatase cytochrome P450 gene expression. This observation may indicate a direct connection between tyrosine phosphorylation and follicle-stimulating hormone (FSH) receptor (FSHR) transduction pathways, as is the case for growth factor receptors with intrinsic tyrosine kinase activity, which share several downstream signaling elements with GPCRs. Some studies leading to our understanding of these pathways are reviewed.

Animals↗

Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic ovary syndrome.

BACKGROUND: The present study was carried out to investigate the functional significance of the reduced dopaminergic tone in subjects affected with polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls (six lean and five obese). In addition, circulating PRL bioactivity was evaluated by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral administration of metoclopramide resulted in a significant increase in serum PRL in all subjects; however, the highest increments, regardless of body mass index (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when compared with all other groups. CONCLUSIONS: These data support the existence of low DA hypothalamic tone in PCOS women that is likely involved in the inappropriate LH and PRL secretion frequently seen in this syndrome. In addition, our results suggest changes in PRL bioactivity in obese PCOS that may play a role in the development of hyperinsulinemia; however, whether PRL has a functional significance in the development of the metabolic disturbances frequently seen in PCOS remains to be elucidated.

Adolescent↗

Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women.

OBJECTIVE: To assess the serum concentrations of estradiol (E2), estrone (E1), gonadotrophins, sex hormone-binding globulin, and lipids, and to determine degree of symptom relief after subcutaneous implantation of 25 mg estradiol in postmenopausal Mexican women. DESIGN: Fifteen postmenopausal, hysterectomized women participated in an open, observational study. Blood samples were obtained before implantation and at regular intervals during a study period of 24 weeks. Climacteric symptoms were evaluated by means of the Greene climacteric scale. Wilcoxon's test was performed on the paired results of pre-and postimplantation values. RESULTS: Serum concentrations of E2 obtained after implantation were fairly constant, remaining within the early follicular range for the entire study period of 24 weeks, and were associated with significant symptom relief. A physiological, premenopausal E2:E1 ratio was achieved. No significant metabolic changes occurred. Side effects were estrogenic in nature and no removal of implant was required. CONCLUSIONS: Subcutaneous implantation of 25 mg estradiol results in physiological, premenopausal estrogen concentrations in most women and is associated with considerable symptom relief without inducing significant adverse metabolic effects.

Estradiol↗

[New paradigms in the regulation of bone metabolism].

Although multiple hormones and cytokines regulate various aspects of osteoclast formation, the two final effectors, osteoprotegerin (OPG) and its ligand (OPGL/RANKL) have been recently identified. Since then, there have been important advances in the understanding of the molecular mechanisms that regulate the crosstalk between osteoblasts/stromal and hematopoietic osteoclast precursor cells. In this article, we describe the new concepts from the identification of OPG, a protein with potent osteoclastogenesis inhibitory activity, to the isolation of RANKL, a transmembrane ligand expressed on osteoblasts/stromal cells that bind to RANK, a transmembrane receptor on osteoclast cells and its precursors. The interaction between RANK and RANKL triggers a series of mechanisms that result in differentiation, maturation and activation of osteoclasts. OPG inhibits osteoclastogenesis binding to RANKL and blocks its interaction with RANK. Many hormones and cytokines, like PTH and IL-11, act inhibiting production of OPG and stimulating production of RANKL. Contrary to this, estrogens inhibit production of RANKL and RANKL-stimulated osteoclastogenesis. The knowledge of the RANK/RANKL/OPG system and the understanding of osteoclast differentiation and activation has had a great impact on the field of bone metabolism, with new possible treatment strategies for diseases characterized by excessive bone resorption.

Animals↗

Reduced dopaminergic inhibition of thyrotropin release in hyperprolactinemic ovulatory women.

It has been suggested that menstrual irregularities in hyperprolactinemia are secondary to an increase in hypothalamic dopaminergic activity via a short loop positive feedback of prolactin (PRL). We have studied this question in a relatively new syndrome characterized by hyperprolactinemia without derangements of the hypothalamic-pituitary-ovarian function due to macroprolactinemia (abnormal high amounts of big-big PRL). Central dopaminergic activity was investigated by the administration of the dopamine antagonist domperidone to normal women (n = 7) and women with anovulatory (n = 6) and ovulatory hyperprolactinemia (n = 2). The effects of domperidone were evaluated in all subjects by the measurements of radioimmunoassayable circulating serum PRL and TSH levels. All subjects had a significant increase in serum PRL levels after 90 min of domperidone administration. Anovulatory hyperprolactinemic subjects showed the highest response to domperidone in terms of TSH, whereas normal women and women with ovulatory hyperprolactinemia had similar increments in TSH serum levels after the administration of the dopamine antagonist. These results support the observation that an increase of hypothalamic dopaminergic activity in hyperprolactinemia may account in part for the presence of menstrual irregularities. The presence of a similar pituitary responsiveness in terms of TSH to domperidone in normal and ovulatory hyperprolactinemic women suggests a similar hypothalamic dopaminergic activity in both group of subjects. These findings might offer an explanation for the coexistence of normal ovulatory cycles in spite of hyperprolactinemia.

Adult↗