Population geometry reveals directed coupling and transient bistability in spontaneous pituitary secretion

Abstract

The pituitary gland operates as an organized signaling network in which endocrine cell populations coordinate hormone secretion, through homotypic and heterotypic interactions, yet the contribution of spontaneous intrinsic activity in shaping population-level dynamics remains poorly understood. Using geometric analysis of population trajectories -- including subspace alignment, manifold separation, and directed coupling metrics -- we identified two classes of spontaneous oscillatory signals associated with distinct cell populations exhibiting asymmetric geometric dominance and a reproducible temporal lag. Our results support that spontaneous activity generates a self-sustained oscillator exhibiting transient bistability, linked to increased physiological demand, with slow oscillations reflecting the properties of an excitatory resonator capable of self-oscillating dynamics without external drive. A low-rank recurrent neural network model recapitulated the empirical geometric landscape under three coupling conditions, confirming that directed population coupling underlies the observed coordination. These findings suggest that intrinsic population dynamics play a central role in coordinating pituitary secretion, with implications for understanding hormonal dysregulation in secretory adenomas and other pituitary disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/716480v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f5e32borg.highwire.dtl.DTLVardef@1151f9eorg.highwire.dtl.DTLVardef@1cefc2corg.highwire.dtl.DTLVardef@ddac4_HPS_FORMAT_FIGEXP M_FIG C_FIG Structural and functional distinctions between homotypic and heterotypic interactions have been widely described in the pituitary endocrine system. However, whether functional differences in intrinsic calcium time-series dynamics are relevant to pulsatile hormone secretion remains unexplored. Here, we classify the spontaneous activity underlying both homotypic and heterotypic interactions and characterise their synchrony. We find that heterotypic interactions exhibit transient bistability, consistent with a Hopf-type oscillator regime, in which slow oscillations drive secretory output according to physiological demand.