MSH is an anti-inflammatory, regulatory hormone made in the hypothalamus. It controls production of hormones, modulates the immune system and controls nerve function, too. It is made when leptin is able to activate its receptor in the proopio-melanocortin (POMC) pathway. If the receptor is damaged by peripheral immune effects, such as the release of too many pro-inflammatory cytokines, then the receptor doesn't work right and MSH isn't made. Leptin controls storage of fatty acids as fat, so MSH and leptin are a major source of interest.
MSH sits as the central hub of a series of important effects. MSH controls hypothalamic production of melatonin and endorphins. Without MSH, deficiency creates chronic non-restful sleep and chronic increased perception of pain, respectively. MSH deficiency causes chronic fatigue and chronic pain. MSH also controls many protective effects in the skin, gut and mucus membranes of the nose and lung. It also controls the peripheral release of cytokines; when there isn't enough MSH, the peripheral inflammatory effects are multiplied. MSH also controls pituitary function, with 60% of MSH deficient patients not having enough antidiuretic hormone. These patients will be thirsty all the time, urinate frequently and often will have unusual sensitivity to static electrical shocks. 40% of MSH deficient patients won't regulate male hormone production and another 40% won't regulate pro-per control of ACTH and cortisol.