11β-HSD1L Activators

Hydroxysteroid 11-beta-dehydrogenase 1-like (11β-HSD1L) activators are a class of chemicals designed to enhance the conversion of inactive cortisone to active cortisol, similar to the function of the well-established enzyme 11β-HSD1. These activators often work indirectly, as there are no well-known direct activators for 11β-HSD1L following the cutoff knowledge date. An increase in the local cortisol levels could suggest that 11β-HSD1L's activity is being enhanced, given that it likely operates within the same pathway as its 11β-HSD1 counterpart. Chemicals such as carbenoxolone and glycyrrhizin inhibit 11β-HSD2, the enzyme responsible for converting cortisol into its inactive form, cortisone. By inhibiting this conversion, these compounds effectively increase the amount of substrate available for 11β-HSD1L to act upon, thereby indirectly enhancing its activity. Other compounds, such as insulin and PGE2, upregulate the expression of 11β-HSD1 in certain tissues, and it's logical to deduce that they may have a similar effect on 11β-HSD1L, leading to an increase in its functional activity.

Additional mechanisms through which the activity of 11β-HSD1L could be enhanced involve the modulation of hormone levels and secondary messengers that affect the enzyme's substrate availability. For example, ACTH stimulates the production of glucocorticoids, which are potential substrates for 11β-HSD1L. Similarly, cAMP, a secondary messenger known to upregulate 11β-HSD1, could also enhance 11β-HSD1L activity. The presence of certain polyphenols like curcumin, as well as components found in fish oil, have been shown to influence 11β-HSD1 and could affect 11β-HSD1L in a similar manner, by altering the cellular redox state or lipid profiles that interact with the enzyme. These mechanisms collectively ensure an elevated conversion rate of cortisone to cortisol, which is the hallmark of enhanced 11β-HSD1L activity.