Allopregnanolone seems to act at several levels of feeding regulation, that is, to initiate feeding and to prolong the duration of a meal, thereby increasing the meal size, especially in the dark period of the 24-h cycle.

Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA receptors (primarily with α3 and α2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA receptor (with compensatory >12-, >5- and >1.5-fold increases in α4, γ2, and α1, α3 subunits), and increases in the α4, βx, δ receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

SummaryThe transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p < 0.025) and DQBI*0302 (p < 0.01) from both parents to the index patient. There was an increased transmission of DQBI*0302 (p < 0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p < 0.01) of positively associated haplotypes (DR4-DQAI* 0301-DQBl*0302, DR3-DQAI*0501-DQBI*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development. [Diabetologia (1994[Diabetologia ( ) 37: 1105[Diabetologia ( -1112

The GABA-site antagonism does not depend on the subtype of alpha-subunits. Similarly, pentobarbital activates ternary receptors composed of different alpha-subunits in a bicuculline-sensitive manner. The potencies of bicuculline to inhibit pentobarbital-activated currents are identical with receptors containing alpha1, alpha4 or alpha5-subunit. The alpha1beta2 and alpha4beta2 receptors possess higher GABA potencies compared with the alpha1beta2gamma2L and alpha4beta2gamma2L receptors.

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