The reproductive endocrine consequences of anorexia nervosa

Leptin, the metabolic fat hormone, has been shown to have effects on reproduction in mice and to modulate steroid production by cultured ovarian somatic cells in a number of species. However, a direct role of leptin on normal ovarian function in vivo has not been shown. In this paper the effect of passive immunisation against leptin (experiment 1; 20 ml antiserum or non-immune plasma i.v.; n 5 6/treatment) and direct ovarian infusion of leptin (experiment 2; 0, 2 or 20 mg recombinant ovine leptin; n 5 4/treatment) during the early follicular phase was investigated in sheep with ovarian autotransplants, which allow recovery of ovarian venous blood and regular non-invasive scanning of the ovary. Passive immunisation against leptin resulted in an acute increase (P < 0.05) in ovarian oestradiol secretion but had no effect on gonadotrophin concentrations, ovulation or subsequent luteal function. Conversely, direct ovarian arterial infusion of the low dose of leptin resulted in an acute decline (P < 0.05) in ovarian oestradiol secretion whereas the high dose, which resulted in supra-physiological leptin concentrations, had no effect on oestradiol production compared with the controls. Neither dose of leptin had any effect on gonadotrophin concentrations or ovulation but both doses resulted in an increase (P < 0.05) in progesterone concentrations over the subsequent luteal phase. In conclusion, together these data provide strong in vivo evidence that leptin can modulate ovarian steroidogenesis directly and acutely in ruminants and suggest that leptin is an alternate regulatory system whereby nutritional status can regulate reproductive activity.

Section: Introductionmentioning

confidence: 99%

Direct in vivo effects of leptin on ovarian steroidogenesis in sheep

Kendall¹,

Gutiérrez²,

Scaramuzzi³

et al. 2004

“…Although ovulation rate is influenced by genetically determined factors, it is also influenced by environmental factors such as nutrition; and ovulation rates can adapt to align with nutritional status. Extreme energy restriction can lead to suppressed development of ovulatory follicles and anoestrus through inhibition of GNRH pulsatility (Jolly et al 1995, McShane et al 1994, Katz & Vollenhoven 2000. However, increasing energy supply over a maintenance level leads to an increase in fecundity by an effect on follicle development and ovulation, which appears to act through a variety of mechanisms at both central and local levels (Scaramuzzi et al 2006).…”

Section: Introductionmentioning

confidence: 99%

The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro

Campbell¹,

Onions²,

Kendall³

et al. 2010

The objective of this study was to investigate the effect of three monosaccharides or pyruvate on the ability of gonadotrophins to induce cellular proliferation and differentiation of cultured sheep granulosa cells. Lactate production and levels of mRNA expression for the glucose transporters SLC2A1, SLC2A4, SLC2A5 and SLC2A8 were also determined. No energy source in the culture media reduced cell number (50%) and oestradiol (E 2 ) production. Dose and type of monosaccharide had a highly significant (P!0.001) effect on FSHinduced differentiation of the granulosa cells, and there was a highly significant interaction (P!0.001). Glucose supported higher levels of E 2 production than fructose, which was in turn higher than galactose (P!0.001). In contrast, pyruvate at low doses supported similar levels of E 2 production as glucose, but higher doses were markedly inhibitory to E 2 production (P!0.001). Cells responded positively to insulin (P!0.001) in the presence of all three monosaccharides. Glucose and the high doses of fructose resulted in the accumulation of lactate (P!0.001), but pyruvate, galactose and the low dose of fructose resulted in low lactate production. SLC2A5 expression was not detected and SLC2A8 expression was not affected, but SLC2A1 and SLC2A4 expression was depressed (P!0.05) by culture in the presence of fructose and glucose. These data show that glucose, metabolised under anoxic conditions to lactate, is the preferred energy substrate to support the gonadotrophin-induced differentiation of ovine granulosa cells in vitro, and that fructose and pyruvate, but not galactose, are alternative energy substrates despite marked differences in the way these substrates are metabolised.

“…Severe under-nutrition is associated with anovulatory infertility (e.g. anorexia nervosa; Katz & Vollenhoven 2000) and negative energy balance is associated with poor fertility (e.g. the high genetic merit dairy cow in early lactation; Butler 2000, de Vries & Veerkamp 2000.…”

Section: Introductionmentioning

confidence: 99%

The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

Campbell¹,

Kendall²,

Onions³

et al. 2010

Glucose is a critical metabolic fuel in most mammals although many foodstuffs also contain high levels of the monosaccharides, galactose and fructose. The aims of this work were to determine the insulin response to challenges of these sugars (experiment 1) and to examine the effect of systemic (experiment 2) and direct ovarian (experiment 3) infusion of these monosaccharides on ovarian function in ewes with autotransplanted ovaries. In experiment 1, both fructose (fourfold increase peaking in 2 h) and galactose (twofold increase; 30 min) elicited markedly different (P!0.001) insulin responses than glucose (sevenfold increase; 20 min) although the total amount released following fructose and glucose challenge was similar. In experiment 2, low-dose systemic fructose infusion had no acute effect on insulin but did depress FSH (P!0.05), and following the end of fructose infusion, a transient increase in FSH and insulin was observed (P!0.05), which was associated with an increase (P!0.05) in ovarian oestradiol and androstenedione secretion. Systemic infusion of neither glucose nor galactose had a significant effect on ovarian steroidogenesis although glucose acutely suppressed insulin levels. In contrast, ovarian arterial infusion of fructose and glucose had no effect on ovarian function whereas galactose suppressed ovarian follicle number and steroid secretion (P!0.05). In conclusion, this work indicates that fructose and galactose can influence ovarian function in vivo in sheep and that different mechanisms are involved. Thus, fructose exerts stimulatory effects through indirect modulation of peripheral insulin and/or gonadotrophin levels whereas galactose exerts primarily suppressive effects by direct actions on the ovary.