Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women

Abstract

Leptin, an adipocyte hormone, is a trophic factor for the reproductive system; however, it is still unknown whether there is a dynamic relation between fluctuations in circulating leptin and hypothalamic-pituitary-ovarian (HPO) axis hormones. To test the hypothesis that fluctuations in plasma leptin concentrations are related to the levels of luteinizing hormone (LH) and estradiol, we sampled plasma from six healthy women every 7 min for 24 h during days 8-11 of the menstrual cycle. Cross-correlation analysis throughout the 24-h cycle revealed a relation between release patterns of leptin and LH, with a lag of 42-84 min but no significant cross-correlation between LH and estradiol. The ultradian fluctuations in leptin levels showed pattern synchrony with those of both LH and estradiol as determined by cross-approximate entropy (crossApEn). At night, as leptin levels rose to their peak, the pulsatility profiles of LH changed significantly and became synchronous with those of leptin. LH pulses were fewer, of longer duration, higher amplitude, and larger area than during the day. Moreover, the synchronicity of LH and leptin occurred late at night, at which time estradiol and leptin also exhibited significantly stronger pattern coupling than during the day. We propose that leptin may regulate the minute-to-minute oscillations in the levels of LH and estradiol, and that the nocturnal rise in leptin may determine the change in nocturnal LH profile in the mid-to-late follicular phase that precedes ovulation. This may explain the disruption of hypothalamic-pituitary-ovarian function that is characteristic of states of low leptin release, such as anorexia nervosa and cachexia.

Synthesis and regulation of sex hormone-binding globulin in obesity

“…40,43 In addition to its possible function in the regulation of tissue metabolism, leptin has modulating effects on the hypothalamic ± pituitary ± adrenal 44 and ± gonadal functions. 45 Diurnal levels of leptin correlate inversely with ACTH and cortisol levels, and an inhibitory effect of leptin on the HPA axis has been demonstrated both in mice 46 and men. 47 ± 49 This phenomenon might offer one explanation for the results presented in this paper.…”

Leptina: o diálogo entre adipócitos e neurônios

“…Talvez a leptina exerça uma ação indireta sobre os neurônios produtores de GnRH porque dois estudos não encontraram expressão combinada de mRNA para Ob-Rb e para GnRH nos mesmos neurônios hipotalâmicos (29,70). Com o intuito de observar as influências da leptina no eixo HHG em mulheres na pré-menopausa, nós determinamos as concentrações séricas da leptina, do LH e do estradiol em 6 voluntárias de peso normal (71). Amostras de sangue foram colhidas a cada 7 minutos por 24 horas durante o final da fase folicular em cada mulher.…”

Integrative physiology of human adipose tissue

“…Leptin secretion may have an Integrative physiology of human adipose tissue KN Frayn et al ultradian pattern 160,161 and show pulsatility with a periodicity of less than 1 h. 162 For such leptin pulsation, it has been suggested that growth hormone pulsation is the pacemaker, 163 but this remains to be proven. Systemic plasma NEFA and glycerol concentrations show pulsatility, 164 as does lipolysis in omental adipose tissue in dogs, arguing for coordinated action of adipose tissue throughout the body.…”