Theoretically, meibum could either undergo de novo synthesis in the acinar cells or be taken up from the bloodstream, or both. The evidence for de novo synthesis is supported, due to the fact that the synthetic enzymes for the components and transesterases to form the final products have been detected either directly or indirectly (mRNA) in acinar cells.
6,7,47 To date, there has been no report providing direct evidence that lipids are taken up from the bloodstream to meibomian glands. Thus, it is most likely that all meibum lipids are synthesized by the meibomian glands. According to the concept of “meibogenesis,”
48,49 the first step of meibogenesis is that cellular synthesis of mono-UFAs, mainly C
18:1 and C
16:1 from C
18:0 and C
16:0, by the rate limiting enzyme stearoyl-CoA desaturase 1 (SCD1).
50 In fact, Miyazaki et al.
51 demonstrated that SCD1 was capable of making C
16:1 and C
18:1, and they also discovered the MG and sebaceous gland atrophy in SCD1 knock-out (KO) mice.
52 It has been reported that high levels of dietary oleate (C
18:1n9) and palmitate (C
16:1) are unable to correct the deficiency of triglyceride, cholesterol ester, and WE in SCD
−/− mice.
52 Hence, SCD1 is essential for meibomian gland as well as meibogenesis. SCD1 gene expression is tightly regulated by various parameters, such as insulin, leptin, sex hormones, and growth factors, etc.
53 Research on the estrogen receptor in KO mice has revealed that estrogen is a negative regulator of SCD1,
54 and following on the findings in that study, it has been reported that the administration of estrogen in humans decreases SCD1 in adipose tissues.
55 In this present study, the FA composition of premenopausal women clearly changed in phase II of the cycle when the P4/E2 became minimal. Increased estrogen at ovulation might have a negative influence on SCD1, thus resulting in increased C
16:0 and C
18:0, as well as decreased C
18:1n9. This change would lead to MGD and/or meibomitis in young women.
25 Androgen, on the other hand, has been identified as an activator of SCD1 in hamsters
56 and rats,
57 but to date, not in mice. Sullivan et al.
58 reported that anti-androgen use is paralleled by significant changes in the FA profiles of neutral lipid fractions in meibomian gland secretions. However, in this present study, testosterone did not seem to have any influence on mono-UFA composition.