Phenotypic characterization of multi-functional somatotropes, mammotropes and gonadotropes of the mouse anterior pituitary

Abstract

The existence of bihormonal anterior pituitary (AP) cells co-storing growth hormone and either prolactin (mammosomatotrope) or gonadotropins (somatogonadotrope) has been described. These cells have been proposed to be involved in "paradoxical" secretion [secretion of an AP hormone induced by a non-related hypothalamic releasing factor (HRH) and transdifferentiation (a phenotypic switch between different cell types without cell division]. Here we combine calcium imaging (to assess HRH responsiveness) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of multifunctional somatotropes, mammotropes and gonadotropes in the normal male and female mouse pituitaries. AP cell phenotypes differed from the classic view, showing multiple HRH-receptor expression and/or hormone storage. Mammosomatotropes represented only 5-6% of somatotropes and were poorly responsive to HRHs, suggesting that their contribution to paradoxical secretion should be very limited. Somatogonadotropes were present only in females and contained adrenocorticotropic hormone. They responded to growth hormone-releasing hormone but failed to respond to gonadotropin-releasing hormone (LHRH). Other polyhormonal cells identified include (1) gonadocorticotropes, restricted to females, where they make up more than 50% of all the gonadotropes and contain other AP hormones; (2) gonadomammotropes, which are present preferentially in female cells and respond to LHRH; and (3) gonadothyrotropes, which are present similarly in male and female pituitaries.

Effect of nutrient restriction on the somatotropes and substance P-immunoreactive cells in the pituitary of the female ovine fetus

“…Studies have shown that the pituitary contains multipotential precursor cells capable of differentiation later in gestation [49]. There is evidence of plasticity, transdifferentiation, and polyhormonal cells in many pituitary cell types [34,[50][51][52].…”

Single cell transcriptomic analysis of the adult mouse pituitary reveals a novel multi-hormone cell cluster and physiologic demand-induced lineage plasticity

“…The function of each lineage is considered as mutually exclusive and under the control of a corresponding set of discrete hypothalamic/pituitary regulatory circuits (Davis et al, 2013;Kelberman et al, 2009;Zhu et al, 2007). However, scattered reports of pituitary cells co-expressing multiple hormones have suggested that the organization and function of the pituitary may be more complex than commonly appreciated (Childs, 2000;Frawley and Boockfor, 1991;Seuntjens et al, 2002a;Villalobos et al, 2004b) and the prevalence and complexity of 'multi-hormone' cells in the adult anterior pituitary has remained undefined on a systematic and global level. Thus, understanding the compositions and functions of pituitary cell lineages and their relationships to hormone expression warrants further study.…”

GnRH-Induced [Ca2+]i-Signalling Patterns in Mouse Gonadotrophs Recorded from Acute Pituitary Slices in vitro

“…These responses, which have not been described in adult gonadotrophs before, are reminiscent of amplitude-modulated, non-oscillatory GnRH responses recorded from immature [28] and cloned pituitary gonadotrophs [29]. Alternatively they could correspond to multi-functional cells, like somato-gonadotrophs, which respond poorly to GnRH [30]. It also remains to be determined if the variation of responses to GnRH within the gonadotroph population is due to intrinsic properties (including the stage of cell maturation or cell cycle).…”