Arturo Zárate

Ovarian refractoriness during lactation in women: Effect of gonadotropin stimulation

This study was to obtain information about the response of the ovari es when stimulated by im gonadotropins in women during lactation and to correlate the hormone changes in an attempt to define the activity of the ovaries during the postpartum period. Patients were 6 normal women aged 17-24 years who were studied for 6 weeks. Lactation was started in all patients immediately after delivery and continued during the study. Human menopausal gonadotropins (HMG) (Pergonal 500) were administered by im injection 3 ampules daily for 5 days starting Day 6 after delivery. Total HMG for each woman was 2250 IU. Levels of total estrogens were determined by the Beling technique. Pregnanediol and pregnanetriol were analyzed in 24-hour urine before gonadotropin stimulation then every 3 days for 2 weeks and then weekly for 4 more weeks. Total gonadotropin activity in urine by bioassay was estimated before stimulation. Daily blood samples were also obtained before stimulation. Plasma FSH was assayed by double-antibody radioimmunoassay. Endometrial biopsies were taken 10 and 30 days after the HMG course. The administration of gonado tropins elicited no significant increase in the output of urinary estrogens pregnanediol or pregnanetriol within 20 days after partuition. Significant changes were not observed in steroid output in the following 4 weeks. In all patients the endometrium remained inactive. Basal body temperature was monophasic type. Menstrual flow did not appear. The FSH values were half of those found during the follicular phase of a normal cycle. Results suggest that the ovaries are refractory during a part of the postpartum and lactation intervals. A relative delayed recovery of the pituitary gondotropin activity is also present.

Upper Body Obesity and Hyperinsulinemia Are Associated with Anovulation

The objective of this study was to determine the effect of body fat distribution and hyperinsulinemia on the occurrence of ovulation. Fifty-six women (20–35 years old) either with overweight or obesity (body mass index ≥25) were studied. They were classified in two groups according to waist/hip ratio (WHR); one with predominance of adiposity in the upper body segment (n = 29, WHR >0.85) and the other with predominant adiposity in the lower body segment (n = 27, WHR ≤0.85). Basal body temperature and serum progesterone were determined in each cycle during 6 months. Serum insulin levels were measured at baseline and 30, 60, 90, 120 and 180 min after a 75-gram oral glucose load. The mean insulin values in response to oral glucose load in patients with upper body segment obesity were significantly higher than those corresponding to women with lower body segment obesity. Furthermore, the ratio between ovulated cycles and all the cycles studied in patients with upper body segment obesity was significantly lower than that observed in patients with lower body segment obesity. Upper body obesity seems to affect the ovulatory process and this may be related to the presence of hyperinsulinemia.

Relationship Between Circulating Adipokines and Insulin Resistance During Pregnancy and Postpartum in Women with Gestational Diabetes

BACKGROUND AND AIMS We undertook this study to assess the relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes mellitus (GDM). METHODS This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30, 6 weeks and 6 months postpartum. Circulating adipokines that were evaluated during the study were leptin, adiponectin, retinol-binding protein-4 (RBP4), and tumor necrosis factor-alpha (TNF-α). RESULTS Women with GDM showed higher insulin resistance measured by HOMA-IR than subjects with normal gestation (2.3 ± 2.3 vs. 1.3 ± 0.95). There was no difference between groups in adipokines; however, in women with a healthy pregnancy, RBP4 was associated with insulin resistance (r = 0.47, p <0.05). At 6 weeks and 6 months postpartum, women with previous GDM exhibited persistent elevated leptin and insulin resistance. RBP4 was associated with insulin resistance only in women with a previous healthy pregnancy (r = 0.51, p <0.05). In addition, progressively impaired glucose tolerance was observed after delivery in women with previous GDM. CONCLUSIONS It was demonstrated that GDM is associated with greater insulin resistance than observed in normal pregnancy; however, adipokines are similar in both groups. RBP4 levels are significantly associated with insulin resistance in healthy women during pregnancy and postpartum. After a pregnancy complicated by GDM, leptin and insulin resistance remain elevated and glucose tolerance worsens.

Transdermal estradiol in menopausal women depresses interleukin-6 without affecting other markers of immune response

Objective: The aim of this study was to analyze the effect of transdermal estradiol replacement therapy (HRT) on immune function in menopausal women. Study Design: A prospective comparative study was carried out in 30 women, aged 48–55 years, who were divided into two groups; 20 of them received transdermal estradiol 50 µg/day during 3 months and 10 who refused to receive HRT served as controls. Serum interleukins were quantified by specific immunoenzymatic assays; in addition, hormones of somatotropin axis and prolactin (PRL) were quantified by IRMA and RIA. Results: Baseline elevated interleukin (IL)-6 levels decreased significantly (p < 0.001) after transdermal HRT as compared with the nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I, growth hormone and PRL levels were unaltered by transdermal HRT. Conclusion: Decrement of IL-6 in parallel with absent effect on some indices of immune activity suggests a beneficial action of transdermal HRT. These findings contrast with those demonstrating an increment of immune response in women taking oral HRT. Thus, the route of administra tion determines the effect of HRT on immune function.

ACTH AND CRF-PRODUCING BRONCHIAL CARCINOID ASSOCIATED WITH CUSHING'S SYNDROME

A young female patient, with clinical and biochemical manifestations of severe hypercorticism and with the presence of a pituitary adenoma shown by computerized tomography, was thought to have Cushings syndrome of hypophysial origin. However, the surgically‐removed pituitary adenoma contained no ACTH, by immunocytology, and hypercorticism persisted after transsphenoidal adenomectomy. The patient died and autopsy demonstrated an ACTH and corticotrophin releasing factor (CRF)‐containing bronchial carcinoid. It can be concluded that bronchial carcinoids can produce ACTH and CRF and can mimic the clinical and biochemical manifestations of pituitary Cushings syndrome. Thus, the localization of the primary site of hypercorticism can be extremely difficult in patients who have an insidious, occult extrapituitary tumour. Further work is required to establish whether CRF plays a role in the causation of Cushings syndrome and whether the simultaneous secretion of this peptide can modify the clinical and biochemical manifestations of the ectopic ACTH syndrome.

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective. The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone. Design. Randomized, double-blind, placebo-controlled study. Participants. Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels. Results: Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm2) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD. Conclusions. Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.

Fetal Malnutrition Affects Hypothalamic Leptin Receptor Expression After Birth in Male Mice

BACKGROUND AND AIMS Epidemiological associations between an adverse intrauterine environment and the induction of obesity in adult life led to the concept of fetal programming whereby an unfavorable prenatal environment induces adaptations that improve fetal survival or prepare the fetus in expectation of a particular range of postnatal environments. However, these adaptations (predictive adaptive responses) may later prove to be a disadvantage when the pre- and postnatal environments show discrepancies. We investigated the effect of maternal restricted diet on body weight and expression of hypothalamic Ob-Rb of the offspring. METHODS Balb C mice were mated after pregnancy and were randomly assigned to control (C) and undernutrition group (UN) groups. Control group was allowed food ad libitum and UN group had a 50% restriction of food intake during gestation. In the present study we assessed changes in hypothalamic Ob-Rb mRNA by RT-PCR in offspring from C and UN groups. RESULTS The offspring of UN at birth showed 17% less body weight compared with C, but at 90 days the UN had a greater body weight than C (p<0.01). The UN group also presented an increase in the expression of Ob-Rb at 90 postnatal days (p<0.01). CONCLUSIONS The results suggest that maternal caloric restriction programs a greater expression of Ob-Rb in the hypothalamus in offspring, as well as a body weight gain that persists into adulthood. In addition, changes in Ob-Rb expression suggest that Ob-Rb mRNA in the hypothalamus is sensitive to fetal undernutrition.

Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause

OBJECTIVE To demonstrate that hypoestrogenism in menopause is in part responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA-S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60 years, were given orally conjugated equine estrogen (CEE) to study the effect on circulating DHEA-S, cortisol and ACTH. DESIGN A prospective, non-blinded study was performed. Hormonal levels were analyzed before and after three cycles of CEE 0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days. RESULTS Low baseline levels of DHEA-S increased significantly after HRT (1.71+/-0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from 3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/-144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta-estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol and DHEA-S (r=0.60). In addition, the correlation was highly significant (P<0.001) between ACTH and DHEA-S at the term of HRT. CONCLUSION HRT increased DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism is present, but further studies are required to clarify the mechanism underlying this process.

Serum leptin and somatotropin components correlate with neonatal birth weight.

Objective: To determine whether cord sera leptin and components of the somatotropin axis – growth hormone (GH), total (t) and free (f) insulin-like growth factor (IGF), IGF-binding protein-3 (IGFBP-3), and insulin – correlate with birth weight. Design: Cross-sectional study of 22 newborns, 12 with normal birth weight (NBW) and 10 with low birth weight (LBW), in a population of healthy mothers with an apparent normal pregnancy. Methods: Paired mother–neonate blood samples were obtained at vaginal delivery in order to measure leptin and the somatotropin axis components. Results: In all cases maternal blood concentrations of leptin, t and fIGF-I, its carrier protein IGFBP-3, and insulin were higher than in the cord sera of the newborns, regardless of their birth weight. On the contrary, maternal GH levels were lower than in their neonates. LBW neonates had decreased levels of leptin, tIGF-I, and IGFBP-3 as compared with those levels in NBW offspring; however, GH concentrations were higher in LBW neonates. Birth weight showed a significant correlation with cord sera leptin, tIGF-I, IGFBP-3, and GH; nevertheless birth weight was neither interrelated with fIGF-I nor with insulin levels. Conclusion: These data demonstrate that birth weight is significantly correlated with both leptin and some components of the somatotropin axis; on the other hand, no correlation was observed between leptin concentrations and each one of the components of the somatotropin axis. It is suggested that fetal leptin and the somatotropin axis cooperate in intrauterine growth and birth weight.

Role of prenatal undernutrition in the expression of serotonin, dopamine and leptin receptors in adult mice: Implications of food intake

Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5-HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutrition-induced prenatal undernutrition (UN) was investigated in mice and the expression of 5-HT1A, dopamine (D)1, D2 and Ob-Rb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5-HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. Ob-Rb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by Ob-Rb, 5-HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.